Search PubMedSearch

Biomedical subjects

Y Inoue

Publications and source records attributed to Y Inoue.

At least 73 records · Page 4Linked to original sources

Persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking mGluR1.

Most of the cerebellar Purkinje cells (PCs) of an adult animal are innervated individually by a single climbing fiber (CF) that forms strong excitatory synapses with the PCs. This one-to-one relationship between a PC and a CF is a consequence of a developmentally regulated regression of the innervation of PCs by CFs. We found that, in mice deficient in the type 1 metabotropic glutamate receptor (mGluR1), the regression of supernumerary CFs ceases by the end of the second postnatal week, which is about one week earlier than in normal mice. Consequently, about one third of PCs in the mGluR1 mutant mice are innervated by multiple CFs in adulthood. We conclude that the regression of CFs normally occurs in two developmental phases and that mGluR1 plays a crucial role in the second phase.

Aging

Determining variations in colonic circulation during aortic surgery.

The aim of this study was to compare transanal Doppler examination, intraoperative angiography via the inferior mesenteric artery, and the inferior mesenteric artery stump pressure measurement during abdominal aortic surgery to assess the collateral circulation to the inferior mesenteric artery bed. Transanal Doppler examination revealed that the collateral circulation depended on the superior mesenteric artery in 25 patients (superior mesenteric artery-dominant group), the inferior mesenteric artery in two patients (inferior mesenteric artery-dominant group), and the internal iliac artery in one patient (internal iliac artery-dominant group). The mean (+/-S.D.) inferior mesenteric artery stump pressure index was 0.65 (+/-0.12) in the superior mesenteric artery-dominant group, which was significantly different from 0.43 (+/-0.00) in the inferior mesenteric artery- and internal iliac artery-dominant groups. The Intraoperative angiography showed the meandering mesenteric artery clearly in the superior mesenteric artery-dominant group. The Transanal Doppler examination as well as inferior mesenteric artery stump pressure measurement were useful methods to assess a dominant artery to the inferior mesenteric artery bed and colonic viability.

Aged

ADP-ribosylated actin as part of the actin monomer pool in rat brain.

Mono-ADP-ribosylation in mammals is poorly understood. In this study, we found mono-ADP-ribosylated actin in rat brains. Mono-ADP-ribosylated actin by ADP-ribosyltransferase or nonenzymatic reaction was shown at a different position from the unmodified actin in the isoelectrical focusing. High-pressure liquid chromatography utilizing a reverse phase (ODS) column separated ADP-ribosylated actin from unmodified actin. In the two-dimensional gel electrophoreses and high-pressure liquid chromatography, the endogenously ADP-ribosylated actin was detected in the supernatant fraction from the rat brain extract, where a nonpolymerizing actin was present after removal of the polymerizing actin. The concentration of NAD and ADP-ribose, after microwave irradiation, was 220 nmol and 150 nmol/g of rat brain tissue. Actin ADP-ribosylated by purified ADP-ribosyltransferase failed to form actin filaments after the addition of Mg2+. Actin ADP-ribosylated by the nonenzymatic reaction could polymerize with the addition of Mg2+. The enzymatically modified actin could form actin filaments after treatment with ADP-ribosylhydrolase but not after treatment with phosphodiesterase. These results suggest that ADP-ribosylated actin by enzymatic or nonenzymatic reaction is one of the sequestering factors in actin-actin binding and is a part of the actin pool in the rat brain.

Actins

A novel ALL-L3 cell line, BALM-16, lacking expression of immunoglobulin chains derived from a patient with hypercalcemia.

A human acute lymphoblastic leukemia (ALL) cell line, BALM-16, was established from the peripheral blood specimen of a patient with B cell ALL L3 type (ALL-L3) in relapse. As with the original leukemia cells, the established line was negative for both cell surface and cytoplasmic immunoglobulin (Ig) chains. Absence of Ig expression was confirmed by Western blotting. Southern blot analysis demonstrated homozygous deletion of the C kappa gene, germ line configuration of the C lambda and rearrangement of IgJH genes. Cytogenetic analysis of both leukemic bone marrow and BALM-16 cells showed the t(8;22)(q24;q11) abnormality which is specifically associated with ALL-L3 and Burkitt lymphoma. The patient's serum showed hypercalcemia, prompting further investigation of the established cell lines which showed parathyroid hormone-related peptide (PTHrP) mRNA detected by reverse-transcriptase polymerase chain reaction. However, PTHrP production was not detected in the culture supernatant. The established cell line, BALM-16, could provide a useful material for analyzing the lack of Ig expression and of clarifying the pathogenesis of this type of B cell malignancy.

Adult

Lymphatic regeneration following microvascular limb replantation: a qualitative and quantitative animal study.

Lymphatic regeneration following unilateral hindlimb autotransplantation was studied in 14 Lewis rats using Technetium-99 radiolabeled sulfur colloid (TC-99) lymphoscintigraphy and compared to the lymphatic pattern exhibited in four unoperated control rats. Control animals demonstrate a reproducible flow of lymph along the deep lymphatic system from the foot, draining into the ipsilateral inguinal nodes, and then up to the para-aortic nodes. Following replantation, lymphatic outflow from the replanted limb begins to occur within 3 to 6 days, reaching normal lymphatic clearance within 12 days. However, the pattern of lymphatic flow is ill-defined, relying on multiple small channels of the superficial lymphatic system. In contrast to controls, at 3 hr post TC-99 injection, lymphatic drainage in replanted rats is via the inguinal and axillary nodal regions bilaterally. This abnormal pattern persisted in the replanted animals for the duration of this study, 160 days. It is evident that lymphatic regeneration in this animal model is associated with a rapid return to normal levels of lymphatic clearance via collateral channels within the subcutaneous tissue. The rapidity with which lymphatic drainage is restored, and its localization within the subcutaneous tissue, can explain why replanted tissues and microvascular free flaps seldom develop lymphedema. In addition, the rat hindlimb replantation model may prove useful for studies of the general mechanisms and specific factors responsible for lymphangiogenesis.

Animals

Ring chromosome 20 and nonconvulsive status epilepticus. A new epileptic syndrome.

Six cases of epilepsy associated with ring chromosome 20 are presented. The study of these cases and 20 cases reported in the literature revealed that they constitute a distinct epileptic syndrome: frequent seizures consisting of a prolonged confusional state, with or without additional motor seizures, and an ictal EEG pattern of long-lasting bilateral paroxysmal high-voltage slow waves with occasional spikes. Neurological examination results were normal, and neuroimaging studies often failed to disclose a brain lesion. The seizures were resistant to antiepileptic drug therapy. Comparison of the electroclinical features of nonconvulsive status epilepticus in six patients with and four patients without ring chromosome 20 revealed that the group with the chromosomal anomaly had more frequent, comparatively brief episodes of confusion associated with a less prominent spike component on the EEG. We propose that epilepsy associated with ring chromosome 20 constitutes a new syndrome that may provide an opportunity to scrutinize a genetic mechanism of epilepsy.

Adolescent

The role of Gcr1p in the transcriptional activation of glycolytic genes in yeast Saccharomyces cerevisiae.

To study the interdependence of Gcr1p and Rap1p, we prepared a series of synthetic regulatory sequences that contained various numbers and combinations of CT-boxes (Gcr1p-binding sites) and RPG-boxes (Rap1p-binding sites). The ability of the synthetic oligonucleotides to function as regulatory sequences was tested using an ENO1-lacZ reporter gene. As observed previously, synthetic oligonucleotides containing both CT- and RPG-boxes conferred strong UAS activity. Likewise, a lone CT-box did not show any UAS activity. By contrast, oligonucleotides containing tandem Ct-boxes but no RPG-box conferred strong promoter activity. This UAS activity was not dependent on position or orientation of the oligonucleotides in the 5' noncoding region. However, it was dependent on both GCR1 and GCR2. These results suggest that the ability of Gcr1p to bind Gcr1p-binding sites in vivo is not absolutely dependent on Rap1p. Eleven independent mutants of GCR1 were isolated that conferred weak UAS activity to a single CT-box. Five mutants has single mutations in Gcr1p's DNA-binding domain and displayed slightly higher affinity for the CT-box. These results support the hypothesis that Gcr1p and Gcr2p play the central role in glycolytic gene expression and that the function of Rap1p is to facilitate the binding of Gcr1p to its target.

Base Sequence

Proton NMR study of triantennary complex type N-linked glycan chains: assignment of proton chemical shifts of the beta-Man residue in a basic unit of the triantennary glycan chain having a GlcNAc beta 1-->6 Man alpha 1-->6 Man beta-->sequence.

The chemical shifts of ring protons of the beta-Man residue in a triantennary complex type N-linked glycan chain having a GlcNAc beta 1-->6(GlcNAc beta 1-->2)Man alpha 1-->6 Man beta sequence were unambiguously determined by two-dimensional proton nuclear magnetic resonance (1H-NMR) spectroscopic methods. The chemical shift of H4 (3.84 ppm) of the beta-Man residue was for the first time revealed to be different from those (approximately 3.77 ppm) of biantennary and alternative type of triantennary glycans having a GlcNAc beta 1-->2 Man alpha 1-->6 Man beta sequence, but quite close to that (3.86 ppm) of a pentaantennary glycan containing a GlcNAc beta 1-->6 residue on the Man alpha 1-->6 Man beta sequence. Thus, the addition of GlcNAc beta 1-->6 residue on the Man-4' residue, whose formation is catalyzed by GlcNAc transferase V, is considered to cause a down-field shift of beta-Man H4 in the complex-type N-glycan chains. One possible explanation of this phenomenon is that the conformation of Man alpha 1-->6 arm is folded back toward the proximal core region, as is the case with the complex-type N-glycan chains with the bisecting GlcNAc residue.

Acetylglucosamine

Occurrence of terminal alpha 2-->8-linked disialylated poly-N-acetyllactosamine chains with Le(X) and I antigenic glycotopes in tetraantennary arms of an N-linked glycoprotein isolated from rainbow trout ovarian fluid.

The Pronase digestion of a 54K glycoprotein present in ovarian fluid of rainbow trout yielded a major glycopeptide. Carbohydrate compositional analysis revealed that this glycopeptide was likely to possess a single large N-glycan chain having low molecular weight oligomers of N-acetylneuraminic acid (oligoNeu5Ac). Structural studies of this glycopeptide revealed novel alpha 2-->8-linked disialylated poly-N-acetyllactosamine chains with Le(X) and I antigenic determinants on the N-linked tetraantennary core glycan. In our recent studies (Kitazume,S., Kitajima,K., Inoue,S., Inoue,Y. and Troy,F.A. (1994) J. Biol. Chem. 269, 10330-10340) we presented evidence that synthesis of alpha 2-->8-linked polysialic acid (polySia) chains is a two-step process in which chain initiation is catalyzed by an alpha 2-->8-sialyltransferase (alpha 2-->8-ST; initiase) that catalyzes synthesis of the first Sia alpha 2-->8-linkage, forming the disialic acid (diSia) unit, Sia alpha 2-->8-Sia alpha 2-->6-Gal-. Chain polymerization is then postulated to be catalyzed by a second enzyme, an alpha 2-->8-polyST ("polymerase") that converts the diSia units to polySia chains. The present structural studies leading to the discovery of alpha 2-->8-linked disialylated units that terminate poly-N-acetyllactosamine chains in an N-linked glycoprotein is further evidence in support of our hypothesis that more than one sialyltransferase activity is required for polySia chain synthesis and polymerization.

Animals

Effect of angiotensin II on arteriovenous shunting assessed by hepatic arterial perfusion scintigraphy.

Angiotensin II (AT II) has been reported to improve drug delivery in intraarterial chemotherapy for hepatic tumors. We studied the effect of this agent on arteriovenous (AV) shunting in the liver. Eleven patients with hepatic tumors and an indwelling catheter in the hepatic artery underwent hepatic arterial perfusion scintigraphy with and without AT II infusion. At baseline, following the administration of technetium-99m macroaggregated albumin (Tc-99m MAA) through the catheter, static images of the upper abdomen and whole-body anterior and posterior images were obtained. Two to 14 days later, AT II was infused via the catheter one minute prior to Tc-99m MAA injection, and imaging was performed in the same way as the baseline study. Visual interpretation of the static images showed improvement of drug delivery to the hepatic tumors in eight of 11 patients and no changes in the remaining patients. The percent injected dose in the lungs assessed quantitatively using the whole-body images increased in all patients, suggesting enhancement of AV shunt flow. It was concluded that intraarterial infusion of AT II increases AV shunting in the liver with better targeting to hepatic tumors.

Adult

Recovery of pancreatic beta-cell function in hemochromatosis: combined treatment with recombinant human erythropoietin and phlebotomy.

A patient with diabetes mellitus caused by secondary hemochromatosis was treated using recombinant human erythropoietin and phlebotomy. A total of 12 g of iron had been infused in the patient because of iron deficiency anemia. Blood glucose level was 17.3 mmol/L, and hemoglobin A1c level was 9.0% at admission. He was treated using phlebotomy (400 mL per week), along with subcutaneous injection of 3,000 U of recombinant human erythropoietin three times a week. After approximately 100 days, a total of 5,500 mL of blood (2.75 g iron) could be removed. Serum ferritin level decreased from 10,000 micrograms/L to 4,807 micrograms/L. Fasting and maximum serum C-peptide immunoreactivity values during 100-g oral glucose tolerance tests were improved from 0.14 nmol/L to 0.42 nmol/L and from 1.84 nmol/L to 2.61 nmol/L, respectively. This case suggests that pancreatic beta-cell recovers in diabetes caused by hemochromatosis by reducing iron overload during a short period.

Aged

A review of mutagenesis studies of angiotensin II type 1 receptor, the three-dimensional receptor model in search of the agonist and antagonist binding site and the hypothesis of a receptor activation mechanism.

OBJECTIVE: To seek the mechanism whereby agonists, competitive antagonists and insurmountable antagonists affect the receptor function differently, by reviewing recent mutagenesis studies of angiotensin II type 1 receptor (AT1) in which the binding of the agonist and antagonists and receptor signaling were affected. AT1 RECEPTOR STRUCTURE AND LIGAND BINDING SITES: We built a model of seven transmembrane spanning domains of the AT1 receptors using bacteriorhodopsin as a template. The carboxy terminal of angiotensin II binds to Lys199 in transmembrane domain 5, whereas the guanidinium group of Arg2 binds to Asp281 in transmembrane domain 7. Results of studies using mutagenesis supporting proposed ligand-docking models are discussed. HYPOTHESIS FOR THE LIGAND-INDUCED RECEPTOR SIGNALING MECHANISM: We submit a set of hypotheses for a mechanism whereby the ligand binding induces changes in the receptor conformation by the rotation of transmembrane helices as the initial event for the subsequent activation of a G protein. In this mechanism antagonists are not capable of rotating the helices but agonists are able to do so, which results in the formation of a hydrogen bond between Asp74 in transmembrane domain 2 and Tyr292 in transmembrane domain 7. This mechanism also provides plausible explanation for the activation of monoamine receptors. COMPETITIVE AND INSURMOUNTABLE ANTAGONISTS: Competitive antagonists share the same binding sites with agonists, but insurmountable antagonists do not, and binding of the latter does not preclude agonist binding, for example, to Asp281. CONCLUSION: This hypothesis of the intrareceptor signaling mechanism and the receptor model indicate that some amino acid residues essential for the signaling play their roles in the intrareceptor activation mechanism, whereas others participate directly in ligand binding.

Animals

No effect of the anticholinergic drugs trihexyphenidyl and biperiden on the plasma concentrations of bromperidol and its reduced metabolite.

Effects of the anticholinergic drugs trihexyphenidyl and biperiden on plasma concentrations of bromperidol and its reduced metabolite were studied. Subjects comprised 20 schizophrenic inpatients taking bromperidol, 6-18 mg/ day for 1-9 weeks. Patients were randomly allocated to one of two treatment sequences: trihexyphenidyl-biperiden (n = 12) or biperiden-trihexyphenidyl (n = 8). Each sequence consisted of two 2-week phases, with no washout period between the two phases. The daily dose of trihexyphenidyl was 8 mg and that of biperiden 6 mg. Plasma concentrations of bromperidol and reduced bromperidol were measured using high-performance liquid chromatography (HPLC). There was no significant difference in plasma bromperidol or reduced bromperidol concentrations among baseline, trihexyphenidyl and biperiden phases: 7.3 +/- 3.7 versus 7.2 +/- 4.1 versus 7.0 +/- 4.3 ng/ml and 2.0 +/- 2.1 versus 2.2 +/- 2.1 versus 1.9 +/- 2.0 ng/ml, respectively. The present study thus suggests that neither trihexyphenidyl nor biperiden affects plasma concentrations of bromperidol and its reduced metabolite.

Adult

Increased plasma concentrations of bromperidol and its reduced metabolite with levomepromazine, but not with thioridazine.

Bromperidol is a close structural analog of haloperidol. The authors studied the effects of levomepromazine and thioridazine, which are frequently added to other neuroleptics as sedatives, on plasma concentrations of bromperidol and its reduced metabolite. The subjects were 26 inpatients with schizophrenia receiving bromperidol, 12 to 24 mg/day, for 1 to 19 weeks. In 10 cases, 50 mg levomepromazine per day and in nine cases, 50 mg thioridazine per day were coadministered for 1 week. In seven cases, both drugs were coadministered with > or = 2-week intervals. Plasma concentrations of bromperidol and reduced bromperidol were measured by a high-performance liquid chromatographic method. Levomepromazine (n = 17) significantly (p < 0.001) increased plasma concentrations of bromperidol (7.3 +/- 4.1 versus 10.2 +/- 4.8 ng/ml) and reduced bromperidol (1.8 +/- 1.4 versus 4.5 +/- 3.3 ng/ml). Thioridazine (n = 16) did not significantly change plasma concentrations of bromperidol (9.1 +/- 5.7 versus 8.6 +/- 5.5 ng/ml), while those of reduced bromperidol could not be measured because of interfering peaks. The current study suggests that levomepromazine, but not thioridazine, increases plasma concentrations of bromperidol and reduced bromperidol by inhibiting the metabolism of these compounds.

Adult

Traumatic aneurysm of the temporal artery: a report of five cases.

Five cases of traumatic aneurysm of the superficial temporal artery are reported. Four patients clearly stated that they had sustained traumatic injuries within 3 months prior to the appearance of the pulsating aneurysms; in the remaining case, more than two years had passed before the appearance of the nodule, and it was without pulsation. Color Doppler echography was very useful for observing the circulation in these aneurysms. Histologically, these cases were pseudoaneurysms composed of small vessels with internal elastic lamina and adjacent connective tissue proliferation, suggesting a break in the arterial wall.

Adolescent