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H Takeshima

Publications and source records attributed to H Takeshima.

At least 109 records · Page 6Linked to original sources
PubMed1997

Partial loss of tolerance liability to morphine analgesia in mice lacking the nociceptin receptor gene.

In mice lacking the nociceptin (or orphanin FQ) receptor gene, when 10 mg/kg of morphine was subcutaneously given, a potent analgesia in the tail pinch test was observed. The analgesic effect of morphine was equivalent among wild-type, heterozygous and homozygous mutant mice. When morphine was given to such mice in a dose of 10 mg/kg once per day for 5 days, wild-type and heterozygous mice showed marked tolerance or reduction in the morphine analgesia on the 5th day, while homozygous mice showed only 50% reduction in the peripheral analgesia of morphine. These findings suggest that nociceptin or its receptor plays important roles in the in vivo mechanism for the development of morphine tolerance.

Analgesics, Opioid↗
PubMed1997

Functional and morphological features of skeletal muscle from mutant mice lacking both type 1 and type 3 ryanodine receptors.

1. We generated mice with targeted disruptions in the genes for both ryanodine receptor type 1 (RyR-1) and type 3 (RyR-3) to study the functional roles of RyR subtypes in skeletal muscle. 2. In permeabilized myocytes lacking both the RyRs, the Ca(2+)-induced Ca2+ release (CICR) mechanism was completely lost, and caffeine failed to induce Ca2+ release. 3. Replacement of potassium methanesulphonate in an experimental intracellular solution with choline chloride resulted in Ca2+ release in the wild-type muscle but not in the mutant muscle lacking RyR-1. 4. The double-mutant mice exhibited more severe muscular degeneration than RyR-1-deficient mice with formation of large vacuoles and swollen mitochondria while structural coupling between T-tubules and the sarcoplasmic reticulum was retained. 5. These results demonstrate that CICR is mediated solely by RyR-1 and RyR-3 in skeletal muscle cells, and suggest that RyR-1 is involved in Cl(-)-induced Ca2+ release. The results also suggest the presence of molecular components other than RyRs responsible for the triad formation. RyR-3 may have a role in the normal morphogenesis of skeletal muscle cells, although functionally it can be replaced by RyR-1.

Animals↗
PubMed1997

Unrestrained nociceptive response and disregulation of hearing ability in mice lacking the nociceptin/orphaninFQ receptor.

In the G-protein-coupled receptor superfamily, the opioid receptor subfamily is constituted of the three distinct opioid receptors (namely delta-, mu- and kappa-subtypes) and the receptor for nociceptin (also designated orphaninFQ). The members of the opioid receptor subfamily were known to mediate a variety of cellular inhibitory effects. The three opioid receptors are known to play central roles in mediating analgesia and many other physiological activities; however, the nociceptin receptor was identified recently and less is known about its physiological roles. Here we report the generation and characterization of mice lacking the nociceptin receptor. The knockout mice showed no significant differences in nociceptive threshold and locomotor activity compared with control mice, but they lost nociceptin-induced behavioral responses. These results indicate that the nociceptin system is not essential for regulation of nociception or locomotor activity. On the other hand, we found insufficient recovery of hearing ability from the adaptation to sound exposure in the mutant mice. Thus, the nociceptin system appears to participate in the regulation of the auditory system.

Animals↗
PubMed1997

A region of the ryanodine receptor critical for excitation-contraction coupling in skeletal muscle.

Ca2+ release mediated by the ryanodine receptor (RyR) regulates many important cell functions including excitation-contraction (E-C) coupling in skeletal muscle, by which membrane depolarization controls the opening of RyR via the dihydropyridine receptor. Among the three RyR subtypes, RyR-1 mediates skeletal muscle E-C coupling, whereas RyR-2 and RyR-3 cannot substitute for RyR-1. We carried out expression experiments using cultured mutant skeletal myocytes not having intrinsic intracellular Ca2+ release channels to study the structure-function relationship of amino acid residues 1303-1406 in RyR-1 (D2 region). In this region the amino acid sequences are highly divergent between RyR-1 and RyR-2, and the corresponding sequence is lacking in RyR-3. Expression of RyR-1 but not of RyR-2 rescued E-C coupling in the mutant cells. Deletion of either the entire D2 region or its N-terminal half from RyR-1 preserved the function of RyR-1 as a Ca2+ release channel but resulted in the loss of E-C coupling. Substitution of the D2 region for the corresponding sequence of RyR-2 had no effect on the function of RyR-1. These results indicate that the presence of the D2 region is critical for E-C coupling in skeletal muscle, although the D2 region alone cannot determine the functional difference between RyR-1 and RyR-2.

Amino Acid Sequence↗
PubMed1997

Protecting spermatogenesis from damage induced by doxorubicin using the luteinizing hormone-releasing hormone agonist leuprorelin: an image analysis study of a rat experimental model.

BACKGROUND: This study was performed to investigate the protective effect of a luteinizing hormone-releasing hormone (LHRH) agonist, leuprorelin, against spermatogenetic damage caused by doxorubicin in rats. METHODS: Sprague-Dawley rats were divided into 4 groups: (1) a control group, (2) a group given LHRH agonist (subcutaneous injections, total dose 9 mg/kg), (3) a group given doxorubicin (intraperitoneal injections, total dose 7.5 mg/kg), and (4) a group given both LHRH agonist (subcutaneous injections, total dose 9 mg/ kg) and doxorubicin (intraperitoneal injections, total dose 7.5 mg/kg). Evaluations were made by measuring body and testicular weights, determining Johnsen's score, and conducting DNA image analysis consisting of DNA content measurement (%1C, %2C, and %4C) by image cytometry. RESULTS: In the group given doxorubicin, the testicular weight was 1.47 +/- 0.24 mg, Johnsen's score was 4.4 +/- 1.2, and image analysis revealed %1C: 33.8 +/- 9.2, %2C: 43.9 +/- 16.3, and %4C: 5.0 +/- 4.4. In the group given both LHRH agonist and doxorubicin, the testicular weight was 1.32 + 0.23, Johnsen's score was 5.90 + 1.6, and image analysis revealed %1C: 46.9 +/- 15.0, %2C: 28.4 +/- 13.3, and %4C: 8.8 +/- 3.5. CONCLUSIONS: The significant prophylactic effect (P < 0.05) of the LHRH agonist against doxorubicin-induced spermatogenetic damage was demonstrated by Johnsen's score and image analysis (%1C, %2C, and %4C).

Animals↗
PubMed1997

Deletion of amino acids 1641-2437 from the foot region of skeletal muscle ryanodine receptor alters the conduction properties of the Ca release channel.

The ryanodine receptor (RyR) of skeletal muscle contains two functional domains: a carboxyl-terminal hydrophobic domain that forms the putative conduction pore of the calcium release channel, and a large cytoplasmic domain that corresponds to the "foot structure." To understand the contribution of the foot structure to the function of the calcium release channel, we studied a RyR deletion mutant, delta(1641-2437)-RyR, in which a region that is rich in glutamate and aspartate residues (a.a. 1641-2437) was removed. The wild-type and delta(1641-2437)-RyR proteins were expressed in a Chinese hamster ovary (CHO) cell line, and functions of single calcium release channels were measured in the lipid bilayer membrane. The wild-type RyR forms functional calcium release channels with a linear current-voltage relationship similar to that of the native channel identified in the sarcoplasmic reticulum membrane of skeletal muscle, whereas the channels formed by delta(1641-2437)-RyR exhibit significant inward rectification, i.e., currents moving from cytoplasm into SR lumen were approximately 20% less than that in the opposite direction. As in to the wt-RyR channel, opening of the delta(1641-2437)-RyR channel has a bell-shaped dependence on the cytoplasmic calcium, but the calcium-dependent activation and inactivation processes of the delta(1641-2437)-RyR channel are shifted to higher calcium concentrations. Our data show that deletion of a.a. 1641-2437 from the foot region of the skeletal muscle RyR results in changes in both ion conduction and calcium-dependent regulation of the calcium release channel.

Animals↗
PubMed1997

Functional calcium release channel formed by the carboxyl-terminal portion of ryanodine receptor.

The ryanodine receptor (RyR) is one of the key proteins involved in excitation-contraction (E-C) coupling in skeletal muscle, where it functions as a Ca2+ release channel in the sarcoplasmic reticulum (SR) membrane. RyR consists of a single polypeptide of approximately 560 kDa normally arranged in a homotetrameric structure, which contains a carboxyl (C)-terminal transmembrane domain and a large amino (N)-terminal cytoplasmic domain. To test whether the carboxyl-terminal portion of RyR is sufficient to form a Ca2+ release channel, we expressed the full-length (RyR-wt) and C-terminal (RyR-C, approximately 130 kDa) RyR proteins in a Chinese hamster ovary (CHO) cell line, and measured their Ca2+ release channel functions in planar lipid bilayer membranes. The single-channel properties of RyR-wt were found to be similar to those of RyR from skeletal muscle SR. The RyR-C protein forms a cation-selective channel that shares some of the channel properties with RyR-wt, including activation by cytoplasmic Ca2+ and regulation by ryanodine. Unlike RyR-wt, which exhibits a linear current-voltage relationship and inactivates at millimolar Ca2+, the channels formed by RyR-C display significant inward rectification and fail to close at high cytoplasmic Ca2+. Our results show that the C-terminal portion of RyR contains structures sufficient to form a functional Ca2+ release channel, but the N-terminal portion of RyR also affects the ion-conduction and calcium-dependent regulation of the Ca2+ release channel.

Animals↗
PubMed1997

Subacute sclerosing panencephalitis and chorioretinitis.

This is a case report of a 10-year-old boy with subacute sclerosing panencephalitis (SSPE). He initially developed visual disturbance and macular degenerative changes of the right eye at the age of 8 years, followed by chorioretinitis of the left eye, and his neurological symptoms deteriorated rapidly from the age of 10 years. He was diagnosed as having SSPE, as judged on cerebrospinal fluid examination for measles virus RNA by reverse transcription-polymerase chain reaction (RT-PCR), at the second stage of Jabbour's classification on admission. Although high intensity lesions were observed in the right occipital and temporal lobes, especially around the optic radiation, on T2-weighted brain MRI before the start of intrathecal interferon-alpha (IFN-alpha) therapy, they had disappeared at about two months after the treatment. Chorioretinitis (and/or macular degeneration) should be considered in the differential diagnosis of SSPE, permitting early IFN therapy.

Child↗
PubMed1997

Ca2+-induced Ca2+ release in Chinese hamster ovary (CHO) cells co-expressing dihydropyridine and ryanodine receptors.

Combined patch-clamp and Fura-2 measurements were performed on chinese hamster ovary (CHO) cells co-expressing two channel proteins involved in skeletal muscle excitation-contraction (E-C) coupling, the ryanodine receptor (RyR)-Ca2+ release channel (in the membrane of internal Ca2+ stores) and the dihydropyridine receptor (DHPR)-Ca2+ channel (in the plasma membrane). To ensure expression of functional L-type Ca+ channels, we expressed alpha2, beta, and gamma DHPR subunits and a chimeric DHPR alpha(i) subunit in which the putative cytoplasmic loop between repeats II and III is of skeletal origin and the remainder is cardiac. There was no clear indication of skeletal-type coupling between the DHPR and the RyR; depolarization failed to induce a Ca2+ transient (CaT) in the absence of extracellular Ca2+ ([Ca2+]o). However, in the presence of [Ca2+]o, depolarization evoked CaTs with a bell-shaped voltage dependence. About 30% of the cells tested exhibited two kinetic components: a fast transient increase in intracellular Ca2+ concentration ([Ca2+]i) (the first component; reaching 95% of its peak <0.6 s after depolarization) followed by a second increase in [Ca2+]i which lasted for 5-10 s (the second component). Our results suggest that the first component primarily reflected Ca2+ influx through Ca2+ channels, whereas the second component resulted from Ca2+ release through the RyR expressed in the membrane of internal Ca2+ stores. However, the onset and the rate of Ca2+ release appeared to be much slower than in native cardiac myocytes, despite a similar activation rate of Ca2+ current. These results suggest that the skeletal muscle RyR isoform supports Ca2+-induced Ca2+ release but that the distance between the DHPRs and the RyRs is, on average, much larger in the cotransfected CHO cells than in cardiac myocytes. We conclude that morphological properties of T-tubules and/or proteins other than the DHPR and the RyR are required for functional "close coupling" like that observed in skeletal or cardiac muscle. Nevertheless, some of our results imply that these two channels are potentially able to directly interact with each other.

Animals↗
PubMed1997

Caffeine-induced release of intracellular Ca2+ from Chinese hamster ovary cells expressing skeletal muscle ryanodine receptor. Effects on full-length and carboxyl-terminal portion of Ca2+ release channels.

The ryanodine receptor (RyR)/Ca2+ release channel is an essential component of excitation-contraction coupling in striated muscle cells. To study the function and regulation of the Ca2+ release channel, we tested the effect of caffeine on the full-length and carboxyl-terminal portion of skeletal muscle RyR expressed in a Chinese hamster ovary (CHO) cell line. Caffeine induced openings of the full length RyR channels in a concentration-dependent manner, but it had no effect on the carboxyl-terminal RyR channels. CHO cells expressing the carboxyl-terminal RyR proteins displayed spontaneous changes of intracellular [Ca2+]. Unlike the native RyR channels in muscle cells, which display localized Ca2+ release events (i.e., "Ca2+ sparks" in cardiac muscle and "local release events" in skeletal muscle), CHO cells expressing the full length RyR proteins did not exhibit detectable spontaneous or caffeine-induced local Ca2+ release events. Our data suggest that the binding site for caffeine is likely to reside within the amino-terminal portion of RyR, and the localized Ca2+ release events observed in muscle cells may involve gating of a group of Ca2+ release channels and/or interaction of RyR with muscle-specific proteins.

Animals↗
PubMed1997

[Assessment of reproducibility and unidimensionality of International Prostate Symptom Score Japanese version].

BACKGROUND: International Prostate Symptom Score (IPSS), which is a self-administered questionnaire consisting of 7 questions with 6 categories, has been used in many countries as the standard scale of subjective urinary symptoms of patients with prostatism. In Japan, although we have already used the Japanese version at daily clinical situations, the reproducibility and validity of it have never been examined. We tried to assess the reproducibility and unidimensionality of the questionnaire. PATIENTS AND METHODS: 64 out-patients with benign prostatic hyperplasia were asked to fill the self-administered questionnaires, first at the hospital, and second at home. RESULTS: The weighted kappa statistics were low in almost all the items (0.10-0.75), so the reproducibility was evaluated to be poor. For as reasons, it was suggested that understandings of Japanese translation and recognition of frequency about chronic urinary symptoms were difficult for the respondents. The results of principal component analysis showed that the item for nocturia measures a different aspect from what the other items measured. So the unidimensionality of the scale was also not confirmed. CONCLUSION: These results suggested that IPSS Japanese version should be further modified, especially on its Japanese translation, and then the unidimensionality should be examined again.

Aged↗
PubMed1997

[The physical, mental and social impacts of telling prostate cancer patients the true diagnosis].

BACKGROUND: Telling cancer patients the true diagnosis is inevitable to acquire informed consent especially in the Western world. In Japan, however, no such consensus has been established yet. We investigated the influence of telling the true diagnosis on QOL of prostate cancer patients. METHODS: We measured physical, mental and social aspect of prostate cancer outpatients by the General Health Questionnaire (GHQ) and the international Prostate Symptom Score (I-PSS). Using the general linear models we tried to explore which variables would attribute to "severe depression", "anxiety and insomnia" and "social dysfunction". RESULTS: No significant differences were found in any of the eight variables (age, performance status, clinical stage, I-PSS and Goldberg's four factors of GHQ) among the two groups that were informed the true diagnosis or not. The correlation structures of "severe depression", "somatic symptoms" and I-PSS are significantly different in the two groups. As a result of the analysis by the GLM, "somatic symptoms", I-PSS and clinical stages had main effect on "severe depression". Also, there was an interaction between the effect of telling the true diagnosis and "somatic symptoms". CONCLUSION: These results suggest that the mental condition of prostate cancer patients remain stable when they are in good physical condition regardless of being informed the true diagnosis or not. However, the patients who weren't told the true diagnosis have a tendency to get depression accompanying deterioration of physical condition. It is therefore considered that telling the true diagnosis makes the patients understand the changes of their physical conditions and help their mind to be stable.

Aged↗
PubMed1997

[Neurofibromatosis type 2 (NF2)].

Neurofibromatosis type 2 (NF2) is an autosomal dominantly inherited disorder, strongly associated with development of benign intracranial tumors, including bilateral vestibular schwannomas and meningiomas. The NF2 gene located on the human chromosome 22q12 was recently cloned, and the protein it encodes (termed merlin/schwannomin) was found to be strikingly similar to the moesin-ezrin-radixin (MER) family of cytoskeleton-associated proteins. Mutations of NF2 gene have been found not only in the NF2 patient but also in NF2-related sporadic tumors such as acoustic schwannomas and meningiomas, suggesting that the NF2 gene functionally acts as a tumor suppressor gene. To elucidate the biological function of merlin, we have detected five merlin binding cellular proteins. The N-terminal region of merlin, the entire merlin-ezrin-radixin-moesin (MERM) homology domain, was found to be essential for binding to all five proteins. Since most reported NF2 mutations in the region were determined to be necessary for binding, the mutations probably impair binding. The majority of NF2 mutations are nonsense mutations or frameshifts that resulted in premature termination of merlin. The lack of these interactions caused by such mutations of NF2 gene may affect the cellular signals, resulting in benign intracranial tumors in NF2 patients.

Chromosomes, Human, Pair 22↗
PubMed1996

Identification and characterization of an endogenous ligand for opioid receptor homologue ROR-C: its involvement in allodynic response to innocuous stimulus.

We reported here purification and characterization of a novel heptadecapeptide in bovine brain as an endogenous ligand for ROR-C, an opioid receptor homologue cloned from rat cerebrum. The amino acid sequence of the peptide that we purified is identical to those recently identified as nociceptin in rat brain and orphanin FQ in porcine brain. The peptide inhibited the forskolin-induced cyclic AMP accumulation in ROR-C expressing Chinese hamster ovary cells. Studies on inhibitory activity of cyclic AMP accumulation and Northern blot analysis showed that the peptide and its precursor mRNA are present in a number of brain regions, less abundant in the spina cord, and negligible in the cerebellum. In situ hybridization analysis revealed that hybridization-positive neurons were distributed in the superficial layer (lamina I) of the dorsal horn and were also interspersed between the tract of Lissauer in the spinal cord. Intrathecal administration of the peptide into conscious mice induced allodynia, a pain response to innocuous tactile stimuli, in a beli-shaped manner. These results demonstrate that the peptide exists in the brain and spinal cord and plays an important role in pain transmission.

Animals↗
PubMed1996

Subtype specificity of the ryanodine receptor for Ca2+ signal amplification in excitation-contraction coupling.

In excitable cells membrane depolarization is translated into intracellular Ca2+ signals. The ryanodine receptor (RyR) amplifies the Ca2+ signal by releasing Ca2+ from the intracellular Ca2+ store upon receipt of a message from the dihydropyridine receptor (DHPR) on the plasma membrane in striated muscle. There are two distinct mechanisms for the amplification of Ca2+ signalling. In cardiac cells depolarization-dependent Ca2+ influx through DHPR triggers Ca2+-induced Ca2+ release via RyR, while in skeletal muscle cells a voltage-induced change in DHPR is thought to be mechanically transmitted, without a requirement for Ca2+ influx, to RyR to cause it to open. In expression experiments using mutant skeletal myocytes lacking an intrinsic subtype of RyR (RyR-1), we demonstrate that RyR-1, but not the cardiac subtype (RyR-2), is capable of supporting skeletal muscle-type coupling. Furthermore, when RyR-2 was expressed in skeletal myocytes, we observed depolarization-independent spontaneous Ca2+ waves and oscillations, which suggests that RyR-2 is prone to regenerative Ca2+ release responses. These results demonstrate functional diversity among RyR subtypes and indicate that the subtype of RyR is the key to Ca2+ signal amplification.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1996

Absence of Ca2+ current facilitation in skeletal muscle of transgenic mice lacking the type 1 ryanodine receptor.

1. Whole-cell patch-clamp recordings were used to study voltage-dependent facilitation of Ca2+ currents and excessive Ca2+ tail current in skeletal myoballs cultured from wild-type and transgenic mice expressing a null mutation of the ryanodine receptor (RyR) type 1 (dyspedic myoballs). 2. Ca2+ current density in dyspedic myoballs was reduced by about 60% compared with wild-type cells, with dihydropyridine-binding capacity largely retained. 3. Strong and long-lasting depolarizations (+80 mV and 600 ms), which normally produce excessive tail currents upon repolarization in control cells, failed to do so in dyspedic myoballs. 4. Dyspedic myoballs also failed to produce both Ca2+ current facilitation and the left shift of the current-voltage (I-V) curve induced by paired-pulse stimulation. 5. We propose that excessive tail currents and facilitation arise from silent Ca2+ channels acting as the voltage sensors in excitation-contraction coupling.

Animals↗
PubMed1996

Generation and characterization of mutant mice lacking ryanodine receptor type 3.

The ryanodine receptor type 3 (RyR-3) functions as a Ca2+-induced Ca2+ release (CICR) channel and is distributed in a wide variety of cell types including skeletal muscle and smooth muscle cells, neurons, and certain non-excitable cells. However, the physiological roles of RyR-3 are totally unclear. To gain an insight into the function of RyR-3 in vivo, we have generated mice lacking RyR-3 by means of the gene targeting technique. The mutant mice thus obtained showed apparently normal growth and reproduction. Although Ca2+-induced Ca2+ release from intracellular Ca2+ stores of the mutant skeletal muscle differed in Ca2+ sensitivity from that of wild-type muscle, excitation-contraction coupling of the mutant muscle seemed to be normal. Moreover, we could not find any significant disturbance in the smooth muscle and lymphocytes from the mutant mice. On the other hand, the mutant mice showed increased locomotor activity, which was about 2-fold greater than that of the control mice. These results indicate that the loss of RyR-3 causes no gross abnormalities and suggest that the lack of RyR-3-mediated Ca2+ signaling results in abnormalities of certain neurons in the central nervous system.

Animals↗