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Biomedical subjects

K Tsutsui

Publications and source records attributed to K Tsutsui.

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

Anthraquinones from Neonauclea calycina and their inhibitory activity against DNA topoisomerase II.

In a series of searches for DNA topoisomerase II inhibitors from naturally occurring compounds, a wood extract of Neonauclea calycina MERR. (Rubiaceae) showed a moderate effect in vitro. Purification of the extract resulted in the isolation of seven known anthraquinones. The structures were characterized as damnacanthal, rubiadin 1-methyl ether, nordamnacanthal, morindone, damnacanthol, lucidin 3-O-primeveroside and morindone 6-O-primeveroside by spectral analysis, respectively. Damnacanthal and morindone showed an intensive inhibitory effect against topoisomerase II (IC50: 20 micrograms/ml and 21 micrograms/ml).

Anthraquinones↗
PubMed1998

Increased plasma granulocyte elastase levels in Behçet's disease.

OBJECTIVE: To assess the role of granulocyte elastase in the development of thromboembolic vasculopathy in patients with Behçet's disease. METHODS: Plasma granulocyte elastase-alpha1-proteinase inhibitor (E-PI) complex levels were measured by ELISA in 11 healthy subjects and 19 patients with Behçet's disease (BD). Eight of 19 patients showed deep vein thrombosis on (99m)technetium-macro-agglutinate albumin venography. Hemostatic variables were measured at the same time. RESULTS: The mean plasma E-PI complex level was significantly higher in the 8 patients with than in the 11 patients without deep vein thrombosis (242 +/- 73 vs 165 +/- 97 ng/ml; p = 0.033). The mean plasma E-PI complex level in the 11 patients without deep vein thrombosis was significantly higher than in controls (165 +/- 97 vs 96 +/- 40 ng/ml; p = 0.038). Plasma E-PI complex levels correlated with the serum plasmin-alpha2-plasmin inhibitor complex levels (r = 0.621, p = 0.0084). CONCLUSION: Plasma E-PI complex levels appear to be a useful marker of thromboembolic vasculopathy in BD.

Antifibrinolytic Agents↗
PubMed1998

Expression of amphiphysin I, an autoantigen of paraneoplastic neurological syndromes, in breast cancer.

Amphiphysin I is a 128 kD protein highly concentrated in nerve terminals, where it has a putative role in endocytosis. It is a dominant autoantigen in patients with stiff-man syndrome associated with breast cancer, as well as in other paraneoplastic autoimmune neurological disorders. To elucidate the connection between amphiphysin I autoimmunity and cancer, we investigated its expression in breast cancer tissue. We report that amphiphysin I was expressed as two isoforms of 128 and 108 kD in the breast cancer of a patient with anti-amphiphysin I antibodies and paraneoplastic sensory neuronopathy. Amphiphysin I was also detectable at variable levels in several other human breast cancer tissues and cell lines and at low levels in normal mammary tissue and a variety of other non-neuronal tissues. The predominant amphiphysin I isoform expressed outside the brain in humans is the 108 kD isoform which represents an alternatively spliced variant of neuronal amphiphysin I missing a 42 amino acid insert. Our study suggests a link between amphiphysin I expression in cancer and amphiphysin I autoimmunity. The enhanced expression of amphiphysin I in some forms of cancer supports the hypothesis that amphiphysin family members may play a role in the biology of cancer cells.

Alternative Splicing↗
PubMed1997

cDNA cloning of a novel amphiphysin isoform and tissue-specific expression of its multiple splice variants.

Amphiphysin, an SH3-domain containing protein concentrated in nerve terminals, is believed to be involved in the synaptic vesicle recycling. We have cloned cDNAs of a novel isoform of amphiphysin (amphiphysin II) by exploiting sequence information for homologous ESTs deposited in databases. At least 9 different subtypes of the isoform with 50-60% amino acid identity to the human amphiphysin were identified by a conventional library screening and PCR amplification of cDNA libraries. Each subtype probably represents a splice variant of a single gene transcript. Analysis of mRNA expression in various tissues by RT-PCR showed that the isoform is ubiquitously distributed. The expression spectrum of the isoform subtypes, however, is significantly different in several tissues examined, suggesting that they are involved in the regulation of endocytic processes that are unique to each cell type.

Amino Acid Sequence↗
PubMed1997

Inhibitory role of prolactin in the downregulation of testicular follicle-stimulating hormone receptors in mice.

Previous studies have shown that follicle-stimulating hormone (FSH) reduced its own receptors (downregulation) in the testis of adult mice. In the present study, we further examined the effect of prolactin (PRL) on the downregulation of testicular FSH receptors using hypophysectomized adult mice. FSH binding per testis increased after hypophysectomy, reaching a peak 5-10 days after the operation, and decreased thereafter. Hypophysectomized mice were given s.c. injections of 100 micrograms ovine PRL (NIADDK-oPRL) and/or 2 micrograms ovine FSH (NIADDK-oFSH) twice daily for 5 or 10 days beginning from 5 or 10 days after hypophysectomy. The 5-day treatment with a combination of oPRL and oFSH maintained the level of testicular FSH binding that was decreased by the treatment with oFSH alone, while the 5-day treatment with oPRL alone did not influence the testicular FSH binding. The change in the FSH binding per Sertoli cell was comparable to that in the binding per testis. A similar result was obtained by the 10-day treatment. Therefore, PRL was suggested to have an inhibitory role in the downregulation of testicular FSH receptors by FSH in adult mice.

Animals↗
PubMed1997

Inhibitory role of opioid peptides in the regulation of aggressive and sexual behaviors in male Japanese quails.

We have recently isolated three opioid peptides, i.e., Met- and Leu-enkephalins and Met-enkephalin-Arg6-Phe7, from the avian brain. Furthermore, electrophysiological studies have shown that the dominant effect of these enkephalins on preoptic and hypothalamic neurons is an inhibition of neuronal activities in the male Japanese quail. The hypothalamus and preoptic area are known to be involved in the control of male reproductive behaviors, such as aggressive and sexual behaviors. To determine the functional role of opioid peptides in these reproductive behaviors, therefore, the present study was undertaken using adult males of the Japanese quail. We examined behavioral changes following an injection of naloxone (0.2, 2.0, and 20.0 nmol), a nonselective opioid receptor antagonist, or D-Ala2-Met5-enkephalinamide (DALA; 0.2, 2.0, and 20.0 nmol), a selective delta opioid receptor agonist, into the preoptic and anterior hypothalamic regions. Naloxone treatment showed a significant increase in the frequency of several aggressive actions and the effect was dose dependent. In contrast, DALA treatment significantly decreased the frequency of aggressive actions in a dose-dependent manner. Similar significant effects of these two drugs were observed in the sexual behavior. These findings provide the first evidence for the role of opioid peptides in the reproductive behaviors in the bird and suggest an inhibitory action of opioid to evoke the behaviors.

Aggression↗
PubMed1997

Demonstration, localization, and development of galanin receptors in the quail oviduct.

We recently isolated an oviposition-inducing peptide that was identified as avian galanin from the oviducts of the Japanese quail. Avian galanin was localized in neural fibers distributed in muscle layers in the uterine and vaginal oviduct regions, and potentiated spontaneous contractions of the uterus and vagina. To elucidate whether an oviposition-inducing effect of avian galanin is due to the direct action on the oviduct, therefore, a specific binding site for avian galanin was determined in the functional quail oviduct in this study. The binding of [125I]iodoavian galanin was primarily located in the oviduct as well as the brain. The galanin binding was specifically inhibited as a function of the concentrations of both avian and rat galanins. The specific binding of avian galanin to the quail oviduct was temperature dependent and reached the maximum level for 1 h at 20 degrees C. In several regions of the oviduct, a higher level of specific galanin binding was observed only in the uterus and vagina. In contrast, the specific binding was low in the isthmus and negligible in the magnum. A similar localization was evident in the functional chicken oviduct. The Scatchard plot analysis of the binding of avian galanin to the uterine preparation revealed that the dissociation constant (Kd) was 0.249 (95% confidence interval, 0.192-0.356) nM, and the number of binding sites was 1.13 (0.99-1.36) fmol per mg tissue, respectively. During development, the galanin-binding sites were apparent in the quail oviduct at 3 weeks of age and the number of binding sites markedly increased between 3 weeks and 3 months of age. However, there was no significant change in the Kd value in the developing quail oviduct. This is the first demonstration of the presence of galanin receptors in the reproductive tract, such as the uterine and vaginal oviduct. The present results suggest that the number of galanin receptors in the oviduct increases during development and that galanin acts directly on the mature uterus and vagina to induce their contractions. This mechanism may be essential to the avian oviposition.

Aging↗
PubMed1997

MR appearance of parasymphseal insufficiency fractures of the os pubis.

OBJECTIVE: To clarify the MRI features of parasymphyseal insufficiency fractures of the os pubis. DESIGN AND PATIENTS: MRI was performed in four postmenopausal women with parasymphyseal insufficiency fractures. The diagnosis was confirmed with plain films in every patient. T1-weighted and T2-weighted images were obtained in four patients using a 1.5-T unit. Postcontrast T1-weighted imaging was also done in three patients. RESULTS AND CONCLUSIONS: MRI of pubic parasymphyseal insufficiency fracture characteristically demonstrates a hyperintense mass lesion with a hypointense rim on T2-weighted imaging, showing peripheral and septal enhancement after contrast administration. It is important to have this entity in mind in patients with osteoporosis, especially in patients with a history of pelvic irradiation for malignant disease, so as not to misinterpret it as a chondroid tumor or bone metastasis.

Aged↗
PubMed1997

Immunohistochemical characterization of the suprachiasmatic nucleus and the intergeniculate leaflet in the hereditary bilaterally microphthalmic rat.

Immunohistochemical observation was performed in the suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL) of hereditary bilaterally microphthalmic rats without the optic nerve on both sides. In the microphthalmic rats, volume of the SCN reduced to ca. 70% of the normal and numbers of the vasoactive intestinal polypeptide (VIP)-like immunoreactive (lir) neurons were significantly decreased. Although the arginine vasopressin (aVP)- and the VIP-lir neurons distributed in the dorsomedial and the ventrolateral part of the SCN, respectively, as reported in the normal one, somatostatin-lir neurons, localizing mainly in a border area between the dorsomedial and the ventrolateral region of the normal SCN, were shifted to the ventral part of the SCN in the microphthalmic rats. The ventral part of the SCN was covered with neuropeptide Y (NPY)-lir fibers in both normal and mutant rats. The IGL was hardly delineated cytologically in the lateral geniculate nucleus (LGN) of the mutant rats. NPY-lir neurons were found in the dorsal part of the ventral LGN, in contrast to their even distribution in the normal IGL. These findings suggest that the IGL-SCN tract remains in the hereditary microphthalmic rats without the retinal projections.

Animals↗
PubMed1997

A monoclonal antibody that recognizes ganglioside GD1b in the rat central nervous system.

A monoclonal antibody (MAb), generated by immunizing BALB/c mice with homogenized bovine retinal tissue, was specific to ganglioside GD1b incorporated into liposome membranes. The antibody (MAb-5G6), classified as IgM, immunostained intensely the perikaryon and processes of motoneurons in the cranial motor nuclei and spinal cord. Spinal and trigeminal ganglion cells were also immunopositive to the MAb. Some fiber tract systems, such as the spinal and mesencephalic trigeminal tracts, the solitary tract and the posterior funiculus, were also immunoreactive to the MAb. These findings suggest that MAb-5G6 labeled specifically neurons with axons extending outside of the central nervous system as a peripheral nerve. The immunoreactive substances were visualized under electron microscopy just beneath the postsynaptic membrane and just inside the plasmalemma of the thick dendrites. No axon terminal was immunolabeled by the MAb. In the rat embryos, immunoreactivity to MAb-5G6 was found in the dorsal and ventral root fibers on the 15th embryonic day (E15). However, cell bodies of the spinal ganglion cells and motoneurons were immunostained by MAb-5G6 at a later stage (E20). The ventral commissure fibers in the floor plate of the spinal cord were transiently immunolabeled during E13-15.

Animals↗
PubMed1997

Expression of a betaine aldehyde dehydrogenase gene in rice, a glycinebetaine nonaccumulator, and possible localization of its protein in peroxisomes.

Betaine aldehyde dehydrogenase (BADH) catalyzes the last step in the plant biosynthetic pathway that leads to glycinebetaine. Rice plants (Oryza sativa L.), albeit considered a typical non-glycinebetaine accumulating species, have been found to express this enzyme at low levels. This observation evokes an interest in phylogenic evolution of the enzyme in the plant kingdom. It is reported here that rice plants possess the ability to take up exogenously added betaine aldehyde through the roots and convert it to glycinebetaine, resulting in an enhanced salt-tolerance of the plants. A gene encoding a putative BADH from the rice genome was also cloned and sequenced. The gene was found to contain 14 introns, and the overall nucleotide sequence of the coding region is c. 78% identical to that of the barley BADH cDNA. Cloning of a partial BADH cDNA from rice was accomplished by reverse transcription-polymerase chain reaction (RT-PCR). The nucleotide sequence of the cloned fragment was found to be identical to the corresponding exon regions of the rice genomic BADH gene. The deduced amino acid sequences of rice and barley BADH both contain a C-terminal tripeptide SKL, a signal known to target preproteins to microbodies. This localization was confirmed by an immuno-gold labeling study of transgenic tobacco harboring barley cDNA, which showed BADH protein inside peroxisomes. Northern blot analysis revealed that the level of BADH mRNA is salt-inducible.

Aldehyde Oxidoreductases↗
PubMed1997

Comparison of accelerated hyperfractionated radiotherapy and conventional radiotherapy for supratentorial malignant glioma.

Between 1988 and 1993, 71 patients with glioblastoma or anaplastic astrocytoma were treated either with accelerated hyperfractionation radiotherapy (1.5 Gy twice daily to a total dose of 69 Gy, n = 35) or with conventional fractionation radiotherapy (1.8 Gy daily to 64.8 Gy, n = 36). Two patients in each group did not complete radiotherapy, leaving 67 evaluable. All patients received the chemotherapeutic regime ACNU intraarterially (50 mg/m2) or intravenously (100 mg/m2) prior to and after radiotherapy. Between 1990 and 1992, 19 patients also received intravenous interferon-beta (3 x 10(6) U, three times weekly) during radiotherapy. The median survival time was 14.5 months for the accelerated hyperfractionation group and 14 months for the conventional fractionation group. The median time to progression was 12 months for the accelerated hyperfractionation group and 9.5 months for the conventional fractionation group. There was no significant difference in either survival (P = 0.89) or progression-free survival (P = 0.25) between the accelerated hyperfractionation and conventional fractionation groups. Interferon therapy was associated with poorer survival. Brain necrosis developed in four out of 10 patients receiving accelerated hyperfractionation radiotherapy plus interferon-beta, but in none of nine patients receiving conventional fractionation radiotherapy plus interferon (P = 0.033). In conclusion, our study failed to demonstrate any possible benefit of accelerated hyperfractionation radiotherapy for malignant glioma. The incidence of brain necrosis may be increased by combining accelerated hyperfractionation radiotherapy and interferon-beta.

Adult↗
PubMed1997

Primary testicular non-Hodgkin's lymphoma: a clinical study and review of the literature.

Non-Hodgkin's lymphoma (NHL) of the testis is a rare disease, and treatment outcome is generally poor. In this retrospective study, we investigated treatment results for testicular NHL in an attempt to develop an effective treatment policy for this disease. The survival rate and characteristics were retrospectively analyzed in eight patients with NHL of the testis who were treated between 1969 and 1991 at Kyoto University Hospital, Department of Radiology. Four patients were at stage IEA, one at stage IIEA, and three at stage IVEA. Of the eight testicular lymphomas, six were classed as intermediate grade lymphomas and two as high-grade lymphomas according to the Working Formulation. All of the eight patients received orchiectomy. Six patients received combined chemotherapy and radiation therapy as the primary treatment for the disease. One patient each was treated with radiation therapy alone or combination chemotherapy alone. The 5-year overall and disease-free survival rate was 45 and 33%, respectively. Even though almost all of the patients had received combination chemotherapy, high incidence of relapse in the central nervous system (CNS) was observed. Prophylactic treatment against such recurrence may be necessary to improve the treatment outcome of patients with testicular NHL.

Adult↗
PubMed1997

cDNA cloning, sequence analysis and expression of a mouse 44-kDa nuclear protein copurified with DNA repair factors for acid-depurinated DNA.

We purified a 44-kDa nuclear protein from salt-extract of permeable mouse ascites sarcoma cells in an effort to isolate factors involved in the repair of acid-depurinated DNA. It was copurified with a major AP endonuclease (APEX nuclease) by sequential column chromatography then further purified by sodium dodecyl sulphate-polyacrylamide gel electrophoresis as a possible DNA repair support factor. Its partial amino acid sequences were determined, and a cDNA clone for the protein was isolated from a mouse T-cell cDNA library using long degenerate oligonucleotide probes deduced from the amino acid sequence. The complete nucleotide sequence of the cDNA (1.7 kilobases) was determined. Northern hybridization using this cDNA detected two transcripts: 1.8 kb being the major one and 2.6 kb being the minor one. The complete amino acid sequence for the protein predicted from the nucleotide sequence of the cDNA indicates that the 44-kDa protein consists of 394 amino acids with a calculated molecular weight of 43,698. In tests performed thus far, the recombinant 44-kDa protein expressed in Escherichia coli has not expressed any repair-support activity. It remains to be analyzed whether the protein attains this activity after appropriate posttranslational modifications. Most parts of the 44-kDa protein cDNA and the deduced amino acid sequence were found to be identical to those of the protein p38-2G4, recently reported as a cell cycle-specifically modulated nuclear protein of 38kDa. The p38-2G4 may be a truncated form of the present 44-kDa protein.

Amino Acid Sequence↗
PubMed1997

Induction of resistance to etoposide and adriamycin in a human glioma cell line treated with antisense oligodeoxynucleotide complementary to the messenger ribonucleic acid of deoxyribonucleic acid topoisomerase II alpha.

Acquisition of resistance to anticancer agents is a serious problem for cancer chemotherapy. The present study analyzed the relationship between expression of the alpha isoform of deoxyribonucleic acid (DNA) topoisomerase II (topo II alpha) and chemosensitivity to topo II inhibitors by modulating the level of topo II alpha expression. A phosphorothioate analogue of an 18-nucleotide oligomer which is complementary to the translation initiation site of the human topo II alpha messenger ribonucleic acid sequence was used to suppress the expression of topo II alpha in a human glioma cell line (U373MG). The topo II alpha activity of the treated cells was reduced to 1/3 of untreated cells in a decatenation assay using kinetoplast DNA. Antisense oligoDNA-treated cells showed mild resistance to the topo II inhibitors, etoposide and adriamycin, of about 2.0 fold and 1.5 fold, respectively, compared to control cells. Only partial reduction in the activity of topo II alpha in the glioma cell line can cause a measurable resistance to topo II inhibitors, implying that the degree of topo II expression is correlated with chemosensitivity to topo II inhibitors.

Antibiotics, Antineoplastic↗
PubMed1996

Localization of galanin and its binding sites in the quail brain.

Avian galanin was first isolated from the chicken intestine, and subsequently we isolated the same peptide from the quail oviduct. Galanin is known to be a multifunctional peptide in the neuroendocrine system in mammals, while little information is available for the galanin action in the central nervous system in birds. In the present study, therefore, we examined the presence and the localization of galanin and its binding sites in the quail brain. The binding of [125I]iodo-avian galanin to brain tissues specifically inhibited as a function of the concentrations of unlabeled avian galanin. In all of the observed brain regions, the number of galanin-binding sites when compared on the basis of unit weight was maximal in the interbrain including the preoptic and hypothalamic regions and minimal in the cerebellum. The Scatchard plot analysis of the galanin binding to the interbrain revealed that the apparent equilibrium constant of dissociation (Kd) was 0.281 (95% confidence interval, 0.234-0.351) nM, suggesting the presence of a single class of high-affinity binding sites. Although galanin-like immunoreactivity was found in several restricted regions throughout the brain, the most intense immunoreaction was present in the diencephalic region. Abundant immunoreactive cell bodies and/or fibers were localized in several preoptic and hypothalamic nuclei, i.e., the nucleus preopticus medialis (POM), the nucleus paraventricularis (PVN), the nucleus periventricularis hypothalami (PHN) and the nucleus infundibuli (IN), that are known to be involved in the control of reproductive behaviors as well as the pituitary hormone secretion. A substantial number of immunoreactive cell bodies and/or fibers was further observed within the septal nuclei in the telencephalon and several mesencephalic nuclei including the nucleus intercollicularis (ICo) involved in the control of vocalizations. These results suggest that avian galanin may act as an important factor to modulate the some reproductive behaviors and/or the pituitary hormone secretion in the bird.

Amino Acid Sequence↗