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Biomedical subjects

H Takeuchi

Publications and source records attributed to H Takeuchi.

At least 91 records · Page 5Linked to original sources
PubMed1998

["Painful legs and moving toes" and muscle cramps spreading to the bilateral legs in a patient with alcoholic polyneuropathy].

A 37-year-old man with alcoholic polyneuropathy showed involuntary movement as intermittent flexion-extension or abduction-adduction of his toes identical to "painful legs and moving toes (PLMT)" and muscle cramps. Regarding the sequential spreading of PLMT and cramps from unilateral to contralateral leg muscles and phasic discharges observed by a needle EMG in the foot muscles during PLMT, we suppose that a spinal or supraspinal mechanism was responsible for the production of those movements. This case showed novel aspects of PLMT which was induced by sensory stimulation of the left lower leg and subsequently initiated cramps. The destruction of the lumbar sympathetic ganglion remarkably ameliorated the spontaneous PLMT and cramps, whereas sensory stimulation of the left lower leg still induced those movements. Therefore, we think that sensory inputs from peripheral nerves played a critical role in the generation of PLMT and cramps, and abnormal activities of spinal sympathetic nerves exacerbated those involuntary movements. Sensory induced PLMT may be a subgroup of this movement disorder.

Adult↗
PubMed1997

Distinct specificity in the binding of inositol phosphates by pleckstrin homology domains of pleckstrin, RAC-protein kinase, diacylglycerol kinase and a new 130 kDa protein.

The pleckstrin homology domains (PH domains) derived from four different proteins, the N-terminal part of pleckstrin, RAC-protein kinase, diacylglycerol kinase and the 130 kDa protein originally cloned as an inositol 1,4,5-trisphosphate binding protein, were analysed for binding of inositol phosphates and derivatives of inositol lipids. The PH domain from pleckstrin bound inositol phosphates according to a number of phosphates on the inositol ring, i.e. more phosphate groups, stronger the binding, but a very limited specificity due to the 2-phosphate was also observed. On the other hand, the PH domains from RAC-protein kinase and diacylglycerol kinase specifically bound inositol 1,3,4,5,6-pentakisphosphate and inositol 1,4,5,6-tetrakisphosphate most strongly. The PH domain from the 130 kDa protein, however, had a preference for inositol 1,4,5-trisphosphate and 1,4,5,6-tetrakisphosphate. Comparison was also made between binding of inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate and soluble derivatives of their corresponding phospholipids. The PH domains examined, except that from pleckstrin, showed a 8- to 42-times higher affinity for inositol 1,4,5-trisphosphate than that for corresponding phosphoinositide derivative. However, all PH domains had similar affinity for inositol 1,3,4,5-tetrakisphosphate compared to the corresponding lipid derivative. The present study supports our previous proposal that inositol phosphates and/or inositol lipids could be important ligands for the PH domain, and therefore inositol phosphates/inositol lipids may have the considerable versatility in the control of diverse cellular function. Which of these potential ligands are physiologically relevant would depend on the binding affinities and their cellular abundance.

Amino Acid Sequence↗
PubMed1997

Inositol 1,4,5-trisphosphate receptor subtypes differentially recognize regioisomers of D-myo-inositol 1,4,5-trisphosphate.

The Ins(1,4,5)P3 regioisomers, Ins(1,4,6)P3 and Ins(1,3,6)P3, which can mimic the 1,4,5-arrangement on the inositol ring of Ins(1,4,5)P3, were examined for Ca2+ release by using four types of saponin-permeabilized cell possessing various abundances of receptor subtypes, with special reference to the relation of potency to receptor subtype. Ins(1,4,6)P3 and Ins(1,3,6)P3 were weak agonists in rat basophilic leukaemic cells (RBL cells), which possess predominantly subtype II receptors, with respective potencies of 1/200 and less than 1/500 that of Ins(1,4,5)P3 [the EC50 values were 0.2, 45 and more than 100 microM for Ins(1,4,5)P3, Ins(1,4,6)P3 and Ins(1,3,6)P3 respectively]. Similar rank order potencies were also evaluated for the displacement of [3H]Ins(1,4,5)P3 bound to RBL cell membranes by these regioisomers. However, they caused Ca2+ release from GH3 rat pituitary cells possessing predominantly subtype I receptors more potently; Ins(1,4,6)P3 and Ins(1,3,6)P3 evoked release at respective concentrations of only one-third and one-twentieth that of Ins(1,4,5)P3 (the EC50 values were 0.4, 1.2 and 8 microM for Ins(1,4,5)P3, Ins(1,4,6)P3 and Ins(1,3,6)P3 respectively). In COS-1 African green-monkey kidney cells, with the relative abundances of 37% of the subtype II and of 62% of the subtype III receptor, potencies of 1/40 and approx. 1/200 for Ins(1, 4,6)P3 and Ins(1,3,6)P3 respectively were exhibited relative to Ins(1,4,5)P3 (the EC50 values were 0.4, 15 and approx. 80 microM for Ins(1,4,5)P3, Ins(1,4,6)P3 and Ins(1,3,6)P3 respectively). In HL-60 human leukaemic cells, in spite of the dominant presence of subtype I receptors (71%), similar respective potencies to those seen with COS-1 cells were exhibited (the EC50 values were 0.3, 15 and approx. 100 microM for Ins(1,4,5)P3, Ins(1,4,6)P3 and Ins(1,3,6)P3 respectively). These results indicate that these regioisomers are the first ligands that distinguish between receptor subtypes; the present observations are of significance for the future design of molecules with enhanced selectivity.

Animals↗
PubMed1997

Ultraviolet resonance Raman spectra of Trp-182 and Trp-189 in bacteriorhodopsin: novel information on the structure of Trp-182 and its steric interaction with retinal.

Ultraviolet (244 nm) resonance Raman spectra of Trp-182 and Trp-189 in bacteriorhodopsin were obtained by subtracting the spectrum of the mutants, Trp-182-->Phe or Trp-189-->Phe, from that of the wild-type. Analysis of the spectra shows that the chi2,1 torsion angle about the Cbeta-C3 bond is +/-93 degrees for Trp-182 and +/-100 degrees for Trp-189. Both Trp residues are moderately hydrogen bonded to proton acceptors at their indolyl nitrogens in hydrophobic environments. The environmental hydrophobicity is particularly strong for Trp-182, as judged from the splitting of the W7 Raman band to a triplet. The Raman information on the structure and environment of Trp-189 is consistent with the molecular model from electron diffraction [Grigorieff et al. (1996) J. Mol. Biol. 259, 393-421]. On the other hand, the chi2,1 angle and the hydrogen-bonding state of Trp-182 found here differ from those in the model structure. Revision of the model to correspond to the Raman findings would require a 60 degrees rotation of the Trp-182 indole ring about the Cbeta-C3 bond toward the chromophore retinal and the presence of a water molecule that is hydrogen bonded to the indolyl nitrogen. The triplet feature of the W7 band of Trp-182 is attributable to unusually strong steric repulsion between the indole ring and the 9- and 13-methyl groups of the retinal. Resonance Raman spectra in the visible suggest that this steric conflict destabilizes the 13-cis isomeric state of the retinal.

Bacteriorhodopsins↗
PubMed1997

Water accessibility to the tryptophan indole N-H sites of gramicidin A transmembrane channel: detection of positional shifts of tryptophans 11 and 13 along the channel axis upon cation binding.

Gramicidin A analogues, in which one of four Trp residues was selectively substituted by carbon-deuterated Trp, were incorporated into phospholipid liposomes and their Raman spectra were recorded in the absence and presence of Na+. Detailed analyses of the Raman spectra have revealed the conformation, strength of hydrophobic interaction, and water accessibility of each individual Trp residue of the gramicidin transmembrane channel. The absolute value of the torsion angle chi2,1 about the CalphaCbeta-C3C2 linkage is found to be 94 degrees +/- 6 degrees in both the cation-free and Na+-bound states. The Trp side chains are generally involved in strong hydrophobic interactions with the lipid acyl chains of the membrane and/or with another Trp residue. The water accessibility to the indole N1H site is in the order Trp-15 > Trp-13 >> Trp-11 > Trp-9 in the cation-free state. In the Na+-bound state, however, the water accessibility significantly decreases for Trp-13 and increases for Trp-11 without change for Trp-15 and -9. The site-specific changes of water accessibility are explained by a combination of positional shifts of Trp-13 and -11 toward the channel center and the channel mouth, respectively. Model building has shown that such positional shifts of Trp indole rings can be linked with deflections of amide C&dbd;O bonds toward the channel pore, suggesting a cation-induced conformational transition of the channel backbone structure.

Cations↗
PubMed1997

Pharmacological studies on YM992, a novel antidepressant with selective serotonin re-uptake inhibitory and 5-HT2A receptor antagonistic activity.

YM992 ((S)-2-[[(7-fluoro-4-indanyl)oxy]methyl]morpholine monohydrochloride) is a novel compound that has selective serotonin (5-hydroxytryptamine, 5-HT) re-uptake inhibition and 5-HT2A receptor antagonistic activity in vivo. YM992, fluoxetine and citalopram showed 5-HT uptake inhibition activity in l-5-hydroxy-tryptophan (l-5-HTP)-treated mice. YM992 and trazodone attenuated 5-HT2A/2C receptor agonist-induced head-twitches in mice, indicating that these drugs had 5-HT2A receptor antagonistic activity. YM992 and amitriptyline were highly active in the mouse tail suspension test. In contrast, fluoxetine and citalopram showed only a tendency to reduce the immobility time. Single treatment with YM992 as well as trazodone and fluoxetine ameliorated the learning deficit of olfactory-bulbectomized rats, whereas citalopram and amitriptyline showed an ameliorative effect only after chronic treatment. Although YM992 has moderate affinity for alpha1-adrenoceptors, alpha1-adrenoceptor antagonism of YM992 in vivo was 10 times weaker than that of trazodone. These results demonstrate that YM992 has 5-HT uptake inhibition and 5-HT2A receptor antagonistic activity in vivo, and suggest that YM992 may be a novel antidepressant with high efficacy in clinical use.

Animals↗
PubMed1997

Lipid structure of cytotoxic granules in living human killer T lymphocytes studied by Raman microspectroscopy.

The structures of cytotoxic granules in interleukin-2-activated human killer T lymphocytes have been investigated by Raman microspectroscopy at a single cell level. The Raman spectra of granules share a common feature that lipid Raman bands are much stronger than the Raman bands due to protein, indicating that one of the main components of the granule is lipid. To analyze the lipid structures of individual granules, relationships between Raman spectra and structures have been examined for a series of triacylgycerols with varied degrees of acyl chain unsaturation. Analysis based on the relationships shows that the granulous lipid is characterized by a high content of cis C=C bond, which ranges from about 1.5 C=C bonds per acyl chain in isolated minor granules and to about 2.2 C=C bonds in clustering major granules. The highly unsaturated lipid of major cytotoxic granules is in sharp contrast to the moderately unsaturated (about one C=C bond per acyl chain) plasma membrane lipid. The large difference in lipid unsaturation between the granule and plasma membrane may have relevance to the role of granulous lipid in packaging cytotoxic proteins inside the granule and preventing them from attacking the killer lymphocyte itself.

Humans↗
PubMed1997

Synchronous multiple colorectal adenocarcinomas.

BACKGROUND: The object of the present work was to characterize clinical features and the quality of preoperative examinations in patients with synchronous colorectal carcinomas, and to compare the incidence of associated benign polyps with our findings in patients with a single malignant lesion. METHODS: A retrospective evaluation of 225 patients with primary colorectal carcinoma revealed 9 cases (4.0%) of synchronous colorectal carcinomas. RESULTS: The synchronous colorectal carcinomas were located in the same anatomical segment in 7 patients and were divided into different segments in 2 patients. The accuracy of preoperative diagnosis was 55.6% by endoscopy alone and 66.7% by double contrast barium enema (DCBE) alone, while the rate was 77.8% when colonoscopy and DCBE were combined. There was a higher incidence of associated benign polyps in the group with synchronous colorectal carcinomas (55.6%) versus 28.7% for a single carcinoma (P < 0.05). The main reason why multiple lesions could not be identified preoperatively was that the distal lesions prevented examination of the proximal lesions. CONCLUSIONS: At the time of surgical resection, it is important to ascertain preoperatively whether or not a second lesion exists. If synchronous polyps are present in patients with synchronous colorectal carcinomas, they should be ablated to reduce the risk of metachronous colorectal carcinoma.

Adenocarcinoma↗
PubMed1997

Acute effects of pioglitazone on glucose metabolism in perfused rat liver.

Pioglitazone, a thiazolidinedone derivative, decreases insulin resistance and improves hyperglycemia in insulin-resistant obese and/or diabetic animals. However, the mechanisms by which hyperglycemia is improved are not well defined. We investigated the effects of pioglitazone on hepatic glucose metabolism using a perfused rat liver model. Perfusion with the buffer containing 1-10 microM pioglitazone for 20 min dose-dependently increased the hepatic fructose 2,6-bisphosphate content, a potent activator of 6-phosphofructo 1-kinase. The fructose 2,6-bisphosphate level after 20 min perfusion with 10 microM pioglitazone was 64.9 +/- 14.5 pmol/mg.protein, significantly higher than the control (48.3 +/- 10.9 pmol/mg.protein). When the liver from a starved for 48 h rat was perfused with the buffer containing 2 mM lactate but no glucose, glucose was generated from lactate via the gluconeogenic pathway and flowed into the effluent perfusate at a constant rate of 31 +/- 0.6 mumol/g.liver/h. The addition of 10 microM pioglitazone decreased the glucose output rate to 19.3 +/- 3.8 mumol/g.liver/h. Dose-dependent inhibition of glucose output by pioglitazone was observed in the 1-10 microM dose range. These results indicate that pioglitazone may not only stimulate glycolysis but also inhibit gluconeogenesis in the liver. These acute and insulin-independent effects on hepatic glucose metabolism may partly account for the diverse anti-diabetic effects of pioglitazone.

Administration, Oral↗
PubMed1997

Detection of latent Epstein-Barr virus (EBV) DNA in paraffin sections of nasopharyngeal carcinomas expressing no EBV-encoded small RNAs using in situ PCR.

In situ hybridization (ISH) with EBER 1 (Epstein-Barrvirus (EBV)-encoded small RNA1) probes is widely used for in situ detection of EBV-infected cells. ISH with an EBER1 probe showed that 10 of 40 NPC cases were negative for EBER1 expression. For in situ detection of EBV DNA, we used in situ PCR method which can detect one copy of EBV DNA per cell. Of the 10 EBER1-negative cases, three cases including one each of well- and poorly differentiated carcinomas and undifferentiated carcinoma were EBV DNA-positive by in situ PCR. The remaining seven were truly negative for the presence of EBV DNA. All the EBV genome-negative NPC cases examined here were histologically classified as poorly differentiated or undifferentiated carcinomas which are known to be closely associated with EBV, indicating the existence of EBV DNA-negative NPC cases, regardless of histological type or differentiation. These results indicate that there are EBV genome-positive NPC cases expressing no EBER1 and that in situ PCR can be suitable for in situ detection of EBV-infected cells, especially those expressing no EBER1 in paraffin sections.

Antisense Elements (Genetics)↗
PubMed1997

Immunosuppressant pharmacodynamics on lymphocytes from healthy subjects and patients with chronic renal failure, nephrosis, and psoriasis: possible implications for individual therapeutic efficacy.

BACKGROUND: In organ transplantation, patients with peripheral blood mononuclear cells (PBMCs) that exhibit resistance to cyclosporine (INN, ciclosporin) or glucocorticoids in vitro are refractory to therapy based on these drugs in vivo. However, detection or distribution of the resistant patients with immunologic disorders remains to be documented. METHODS: Drug sensitivity tests were performed with PBMCs from four subject groups: 69 healthy subjects, 100 patients with chronic renal failure, 38 patients with nephrosis, and 51 patients with psoriasis. The values for the concentration that produces 50% lymphocyte-mitosis inhibition (IC50) of the drugs on PBMC blastogenesis were estimated, and individual variations or group differences in the IC50 values were examined. RESULTS: The median cyclosporine IC50 values of the four subject groups were similar, but large individual deviations in the IC50 values were observed. Individual differences in prednisolone IC50 values were spread from 1 to 3500 ng/ml. When compared with healthy subjects, a significantly large number of the patients with chronic renal failure group exhibited low responses to prednisolone (p < 0.04). In contrast, no significant difference in the methylprednisolone IC50 was observed among the groups. Normal upper thresholds for IC50 values of these drugs were estimated from the mean + 2 standard deviations (SD) of the IC50 values of healthy PBMCs, and the patients with IC50 values above these levels were considered to be resistant. The incidence of resistant patients with nephrosis or psoriasis was similar to that of healthy subjects; however, the incidence of cyclosporine- or prednisolone-resistant subjects with chronic renal failure was significantly higher (p < 0.04). Significant correlations between PBMC sensitivity to cyclosporine in vitro and clinical efficacy of the drug in vivo were observed in renal transplant recipients and in patients with psoriasis. CONCLUSIONS: A large subset of patients with chronic renal failure showed PBMC resistance to cyclosporine and prednisolone. Hyperresistant patients have a high risk of being refractory to immunosuppressive therapy with one of these drugs. Alternative treatment should be considered according to the individual drug-sensitivity data.

Adult↗
PubMed1997

Prediction of recurrence in histologically benign meningiomas: proliferating cell nuclear antigen and Ki-67 immunohistochemical study.

BACKGROUND: Recurrence in individual patients after complete surgical removal of meningiomas cannot be predicted by histology alone because recurrence occurs even in histologically benign meningiomas. METHODS: We investigated proliferating cell nuclear antigen (PCNA) and Ki-67 labeling indices of histologically benign meningiomas in 95 patients to assess their relationship to recurrence. The labeling index (LI) was expressed as the percentage of tumor cell nuclei immunoreactive for PCNA or Ki-67 to total tumor nuclei counted per section. The cases/specimens comprised the following two groups: (1) nonrecurrent group: 82 specimens from 82 patients without recurrence, (2) recurrent group: 28 specimens from 10 patients with recurrence. RESULTS: Proliferative activities or aggressiveness do not always develop with every recurrence in recurrent meningiomas. The PCNA LI was significantly higher in the recurrent group (3.98% +/- 0.37%) than in the nonrecurrent group (0.71 +/- 0.13%) (p < 0.0001). The Ki-67 LI also was significantly higher in the recurrent group (3.15 +/- 0.40%) than in the nonrecurrent group (0.39 +/- 0.07%) (p < 0.0001). There was a good correlation between the PCNA LI and the Ki-67 LI (coefficient of correlation r = 0.79, p < 0.001). CONCLUSIONS: The results of our study suggested that a PCNA or Ki-67 LI of more than 2% may represent an increased risk for recurrence; therefore, we suggest that radiotherapy or stereotactic radiosurgery should be considered, even for histologically benign meningiomas.

Adolescent↗
PubMed1997

In vivo study of a calcium phosphate cement consisting of alpha-tricalcium phosphate/dicalcium phosphate dibasic/tetracalcium phosphate monoxide.

Prehardened calcium phosphate cement consisting of alpha-tricalcium phosphate (alpha-TCP), dicalcium phosphate dibasic (DCPD) and tetracalcium phosphate monoxide (TeCP) was implanted in rabbit mandibles and back muscles, and studied histologically and microradiographically. In the mandibles, new bone formation occurred around the implants and increased in quantity the longer the implant period lasted. Histology, microradiography and scanning electron microscopy (SEM) demonstrated direct contact of bone and cement. Bone response to this cement was essentially the same as to hydroxyapatite (HA) ceramics, known as a biocompatible bone substitute. Material resorption was recognized, which increased with the implant period and was greater in the surface bound by soft tissue than the surface bound by bone tissue. In the back muscles, however, no calcified tissue formation occurred. Resorption proved to be faster than in the case of the mandible implants. It was concluded that the cement, in prehardened form, has good biocompatibility and is a promising material as a bone substitute.

Animals↗
PubMed1997

Glucocorticoid-resistance in peripheral-blood lymphocytes does not correlate with number of affinity of glucocorticoid-receptors in chronic renal failure patients.

Glucocorticoid (GC) resistance in patients with chronic renal failure (CRF) seriously impairs successive GC therapy after renal transplantation. We examined the relationship between GC-receptor (GC-R) parameters in peripheral-blood mononuclear cells (PBMC) and PBMC resistance to GC in 21 CRF patients and 18 healthy subjects. Each subject group was divided into two subgroups according to PBMC sensitivity to prednisolone in a mitogen assay procedure; i.e., sensitive (IC50 < 381 ng/mL) and resistant (IC50 > 381 ng/mL) groups. In healthy subjects, the mean GC-R Bmax and Kd in quiescent PBMC of the GC-sensitive group were 2.89 +/- 1.23 fmol/10(6) cells and 4.00 +/- 2.24 nM, respectively. The Bmax in these subjects significantly increased to 6.61 +/- 2.02 (257.7 +/- 107.8%) after 24 h stimulation with concanavalin A (p < 0.01), while the Kd change was not significant. The GC-R Bmax and Kd in quiescent PBMC of the GC-resistant group were 5.33 +/- 1.37 fmol/10(6) cells and 3.20 +/- 1.39 nM, respectively. Both of these parameters, however, did not change significantly after mitogen stimulation. There was a significant negative correlation between IC50S of prednisolone and increase-ratios (post/pre ratio) of Bmax after mitogen stimulation (p < 0.05). In CRF patients, Bmax and Kd in quiescent PBMC of the GC-sensitive group were 6.04 +/- 2.35 fmol/10(6) cells and 3.49 +/- 1.72 nM, respectively, while those in PBMC of the GC-resistant group were 5.13 +/- 2.31 fmol/10(6) cells and 4.04 +/- 1.62 nM, respectively. The Bmax and Kd were not significantly changed after mitogen stimulation in both subgroups of CRF. Moreover, in contrast to healthy subjects, there was no correlation between IC50 and GC-R parameters in CRF. We concluded that, in healthy subjects, decreased PBMC capacity to amplify GC-R numbers in response to mitogen is correlated with GC resistance, whereas in CRF patients the resistant mechanism is not correlated with GC-R parameters. An unknown event might be involved in GC-resistance of CRF.

Adult↗
PubMed1997

Glucocorticoids and cyclosporine induce apoptosis in mitogen-activated human peripheral mononuclear cells.

Induction of apoptosis by immunosuppressive agents such as glucocorticoids (GCs) and cyclosporine (CsA) in cultured lymphoid cells has been suggested. However, there are few studies which demonstrate the induction of apoptosis by these agents in the activation process of human peripheral blood mononuclear cells (PBMCs). Here we show that potent immunosuppressive GCs and CsA induce apoptosis in concanavalin A (con A)-activated human PBMCs. In this study, GCs and CsA suppressed human PBMC-blastogenesis when activated by con A in a dose-dependent manner, where healthy PBMCs treated with > 100 ng/ml of each immunosuppressive agent exhibited a DNA-ladder structure in electrophoretic analysis. In three chronic renal failure (CRF) patients, dose-dependency of the PBMC-apoptosis induction was confirmed by our quantification of fragmented DNA using ELISA. Furthermore, the enrichment of DNA fragmentation was significantly associated with the rate of PBMC-blastogenesis when treated with GCs or CsA (r = -0.466, P < 0.01). These results suggested that suppression of the mitogen-induced PBMC-blastogenesis by the immunosuppressive agents should be correlated with the induction of apoptosis.

Apoptosis↗
PubMed1997

Enhanced amplitude reduction of somatosensory evoked potentials by voluntary movement in the elderly.

We studied the effects of aging on modification of the median nerve somatosensory evoked potentials (SEPs) by voluntary movement in 17 aged (66.5 +/- 8.9 years, mean +/- SD) and 12 young normal humans (27.5 +/- 5.0 years). The amplitudes of cortical SEP components were generally larger in the aged group than in the young group. Following isometric contraction of the thenar muscle, the aged group showed significant attenuation of the prerolandic P22-N28-P45 and the postrolandic P24-N30-P45, while the young group only demonstrated significant reduction of the prerolandic P22-N28 amplitude. In the prerolandic N28-P45 and the postrolandic P24-N30 and N30-P45, amplitudes reduced by voluntary movement (gated amplitude) significantly correlated with amplitudes at rest (resting amplitude) and with the age of subjects. The effects of stimulus intensity and frequency on gating supported the correlative changes between gated and resting amplitudes. These results suggest that the magnitude of gating depends on SEP amplitudes at rest, and that augmented gating in the aged group is a result of enlarged SEPs. Since the cervical and Erb's potentials were not changed by movement, and passive movement did not significantly affect the SEPs, a centrifugal mechanism is probably responsible for gating in this study.

Adult↗