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Biomedical subjects

T Shioiri

Publications and source records attributed to T Shioiri.

At least 55 records · Page 3Linked to original sources

Prevalence of cavum septum pellucidum detected by MRI in patients with bipolar disorder, major depression and schizophrenia.

The incidence of cavum septum pellucidum (CSP), which has been widely regarded as a developmental anomaly of little clinical importance in neuropathology, was examined in 113 patients with affective disorders (69 with bipolar disorder and 44 with major depression), 40 schizophrenic patients, and 92 control subjects by magnetic resonance imaging (MRI). Significantly higher incidence of Grade 3-4 CSP (moderate to large) compared with the controls was found only in the schizophrenics. When a broader interpretation of CSP, including indeterminant (Grade 1) and small (Grade 2) CSP was used, three additional patients with bipolar disorder were found to have Grade 1-2 CSP, and the total prevalence of Grade 1-4 CSP in the patients with bipolar disorder was significantly higher than that in the control subjects but slightly lower than that in the schizophrenic patients. CSP was not observed in any patient with major depression. There were no differences between the patients with and without CSP in age, sex, education, or the duration of illness. These findings are consistent with the hypothesis that neurodevelopmental abnormality may be present in schizophrenia, and such an abnormality may also be present in some patients with bipolar disorder.

Adult↗

The symptom structure of panic disorder: a trial using factor and cluster analysis.

Using cluster analysis of 207 patients with panic disorder (PD), we investigated the relationships between several panic symptoms at the time of panic attacks, which included anticipatory anxiety, agoraphobia, and 13 clinical symptoms based on the Diagnostic and Statistics Manual-III-Revised. Cluster analysis revealed three panic symptom clusters: cluster A (dyspnea, choking, sweating, nausea, flushes/chills); cluster B (dizziness, palpitations, trembling or shaking, depersonalization, agoraphobia, and anticipatory anxiety); and cluster C (fear of dying, fear of going crazy, paresthesias, and chest pain or discomfort). Generally, cluster A was comprised exclusively of physiological symptoms, among which respiratory symptoms were prominent, cluster B included both panic and non-panic symptoms such as agoraphobia and anticipatory anxiety, and cluster C was comprised chiefly of fear symptoms.

Adult↗

Effect of pharmacotherapy on serum cholesterol levels in patients with panic disorder.

It is unclear whether elevated cholesterol level is a complication of panic disorder (PD) or is associated with pharmacotherapy. We compared the total cholesterol (TC) level in 47 PD patients with that in 47 gender- and age-matched normal controls (NC), and we also examined the pre- and post-treatment TC levels. There was no sex difference in TC. Before pharmacotherapy, the mean TC level in the PD group (194.9 +/- 39.6 mg/dl) was non-significantly higher than that in the NC group (190.5 +/- 26.7 mg/dl). The mean TC level in the PD group was significantly reduced following the pharmacotherapy (post-TC: 184.7 +/- 31.0 mg/dl; t = 2.44, P < 0.02), and the subgroup treated with alprazolam (n = 26) showed markedly significant decrease of TC after the treatment (t = 2.36, P < 0.03). The TC level in the PD subgroup with agoraphobia (n = 24, 198.9 +/- 37.9 mg/dl) was slightly higher than that in the group without agoraphobia (n = 23, 190.8 +/- 41.6 mg/dl). These findings suggest that there is a relationship between cholesterol levels and treatment in PD.

Adult↗

Effect of photic stimulation on energy metabolism in the human brain measured by 31P-MR spectroscopy.

Effect of photic stimulation (PS) on energy metabolism in the human occipital cortex was examined by using phosphorus-31 magnetic resonance spectroscopy in 9 normal subjects. Phosphocreatine (PCr)/total phosphorus signal peak area ratio significantly decreased from 12.3% to 10.9% during the 12 minutes of PS (P < 0.05). PCr once returned to a normal level after PS (11.9%) but significantly decreased again 12-18 minutes after PS (10.8%; P < 0.05). Intracellular pH increased from 7.08 to 7.16 during PS, although this increase was not significant. These results suggest that functional alteration of energy metabolism in the brain is different from that in muscles.

Adult↗

Choline-containing compounds detected by proton magnetic resonance spectroscopy in the basal ganglia in bipolar disorder.

Choline-containing compounds (Cho) were examined by proton magnetic resonance spectroscopy (1H-MRS) in the left subcortical region, including basal ganglia, in 19 euthymic patients with bipolar disorder and 19 age-matched normal controls. Ten of the patients were treated with lithium; the remaining 9 were not treated with lithium for at least 30 d. The Cho to creatine + phosphocreatine (Cr) peak ratio in the bipolar patients (0.75 +/- 0.38 [mean +/- SD]) was higher than that in the normal controls (0.52 +/- 0.26, P < 0.05). There was no significant difference in the Cho:Cr peak ratio between patients treated with lithium (0.63 +/- 0.36) and without lithium (0.89 +/- 0.35). These results do not support the hypothesis that lithium increases the brain choline-containing compounds, but rather imply that membrane breakdown may occur in the basal ganglia of patients with bipolar disorder.

Adult↗

Lateralized abnormality of high-energy phosphate and bilateral reduction of phosphomonoester measured by phosphorus-31 magnetic resonance spectroscopy of the frontal lobes in schizophrenia.

Magnetic resonance spectroscopy (one-dimensional chemical shift imaging) was used to measure membrane phospholipid metabolism and high-energy phosphate metabolism in the left and right frontal lobes of 27 schizophrenic patients. In the schizophrenic patients, the phosphomonoester peak area was decreased in bilateral frontal lobes compared with that in age-matched normal subjects. On the other hand, the peak area of beta-adenosine triphosphate was increased in the left frontal lobe in the schizophrenic group. The phosphocreatine peak area was increased in the left frontal lobe of schizophrenic patients with high scores on the Scale for the Assessment of Negative Symptoms (SANS).

Adenosine Triphosphate↗

Wide difference between the cytotoxicity of the 11-alpha-and 11-beta-cyano analogues of tilivalline and their epimeric conversion.

Tilivalline (TV) possesses a pyrrolo[1,4]benzodiazepine nucleus and is cytotoxic toward mammalian cells. The 11-beta-cyano TV analogue (1) is about one hundred times more cytotoxic to mouse leukemia L1210 cells than TV itself. In contrast, the 11-alpha-cyano TV analogue (2), an epimer of 1, has only about one-hundredth the cytotoxicity of 1. It was found that epimerization proceeded between 1 and 2 under physiological conditions, and the cytotoxicity of 2 is thought to be caused mainly by 1 that was formed from 2 during incubation in medium.

Animals↗

Conformational analysis of dolastatin 10: an NMR and theoretical approach.

A solution conformational analysis of dolastatin 10, a powerful antineoplastic agent, has been carried out by means of nmr techniques and theoretical calculations. 1H mono- and bidimensional nmr experiments, as well as 1H-13C heterocorrelated spectra, have been performed on CD2Cl2 solutions. The most interesting nmr data is a huge shielding of the aCH(25) proton of the Dov residue, suggesting the presence of an interaction between the N-terminal and the aromatic C-terminal ends of the molecule. The possibility of a head-to-tail intermolecular association having been discarded, the presence of a series of preferred folded conformation has been hypothesized. Conformational theoretical analysis supports the nmr hypothesis of a folded peptide-like molecule, and a series of possible conformers in good agreement with the experimental data have been analyzed.

Amino Acid Sequence↗

Lateralized abnormality of high energy phosphate metabolism in the frontal lobes of patients with bipolar disorder detected by phase-encoded 31P-MRS.

High energy phosphate metabolites were measured using phase-encoded in vivo phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in both the left and right frontal lobes of 25 patients with bipolar disorder. Eleven patients were examined in the depressive state, 12 in the manic state, and 21 in the euthymic state. Twenty-one age-matched normal volunteers were also examined. The phosphocreatine (PCr) peak area percentage in the left frontal lobe in the patients in the depressive state was decreased compared with that in the normal controls. It was significantly negatively correlated with the Hamilton Rating Scale for Depression score evaluated at the time of 31P-MRS examination. The PCr peak area percentage in the right frontal lobe in the patients in the manic and the euthymic states was decreased compared with that in the controls. These results are compatible with previous reports describing reduction of glucose metabolism in the left frontal lobe in depressive patients with bipolar disorder and trait-dependent right hemisphere dysfunction in bipolar disorder.

Arousal↗

[A stereoselective synthesis of tilivalline and its analogs utilizing a new Mannich type intramolecular cyclization].

Tilivalline (1a), a metabolite isolated from Klebsiella pneumoniae var. oxytoca, belongs to a group of pyrrolo[2,1-c][1,4]benzodiazepines, a characteristic skeleton of anthramycin-type antitumor antibiotics. We have accomplished a completely stereoselective, efficient and convenient synthesis of 1a utilizing a new Mannich type intramolecular cyclization as a key step. Further, a computational chemical analysis clarified the effect of zinc chloride on the high stereoselectivity in the tilivalline synthesis. To aim both the extension of the scope of the new Mannich type intramolecular cyclization and the studies on the structure-biological activity relationship, we further extended the method to the synthesis of tilivalline derivatives and 2-(3'-indolyl)-1,4-benzodiazepines (50). Investigation on the cytotoxicity of 1a and its analogs has revealed that 1a shows the strong cytotoxicity toward mouse leukemia L 1210 cells and the replacement of the indole function of 1a with cyano one increases the cytotoxicity of 1a about 100 times (IC50 = 0.05 microgram/ml).

Animals↗

Structure-cytotoxicity relationship of tilivalline derivatives.

Tilivalline (TV) possesses a pyrrolo[1,4]benzodiazepine nucleus and an indole substituent in its structure, and is cytotoxic toward mouse leukemia L1210 cells. In order to obtain more effective compounds, we have previously synthesized a variety of TV analogues. In this study, the cytotoxicity of these compounds has been evaluated. Among the compounds tested, the 11-beta-cyano compound, a TV analogue bearing the cyano group instead of the indole group, is approximately 100 times more cytotoxic than TV itself. The alpha-epimer of this cyano compound has about one-hundredth the cytotoxicity of the 11-beta-cyano compound. Structure-cytotoxicity relationships are discussed, including the effects of stereoisomers (alpha and beta) at the 11 position and substitution at the benzene moiety of TV.

Animals↗

Structure of ascidiacyclamide as the ethanol water solvate, a cytotoxic cyclic peptide from Ascidian.

The X-ray crystal structure determination of the C2H5OH.H2O solvate of ascidiacyclamide (C36H52N8O6S2), a cytotoxic cyclic peptide from marine tunicate Ascidian, revealed a C2-symmetric saddle-shaped rectangular conformation of the molecule. The water and ethanol molecules are located on the crystallographic diad axis and are held by hydrogen bonds and van der Waals contacts with the polar ring N atoms and nonpolar D-Val side-chain atoms, respectively. The molecular conformation and the interaction with solvent molecules are nearly the same as those of the compound with C2H5OH.2H2O [Ishida, In, Doi, Inoue, Hamada & Shioiri (1992). Biopolymers, 32, 131-143].

Animals↗

Patellamide A, a cytotoxic cyclic peptide from the ascidian Lissoclinum patella.

The structure of crystals of patellamide A (13-methyl-9,23-bis(1-methylethyl)-2,16-bis(1-methylpropyl)-14,-28-di oxa-7,21- dithia-3,10,17,24,29,30,31,32- octaaza-pentacyclo[24.2.1.1(5,8).1(12,15).1(19,22]dotriac onta-1(29),5,- 8(30),15(31),19,22(32)-hexaene-4,11,18,25-tetraone methanol solvate monohydrate, C35H49N8O6S2.-CH4O.H2O), a cytotoxic cyclic peptide having a non-C2-symmetric methyl group, shows the C2-symmetric and saddle-shaped rectangular conformation where the methyl group is disordered into two C2-symmetric positions. The water and methanol solvents were located on the crystallographic diad axis and were held by hydrogen bonds and van der Waals contacts with the polar ring N atoms and non-polar D-Val side-chain atoms, respectively.

Animals↗

Interaction of marine toxin dolastatin 10 with porcine brain tubulin: competitive inhibition of rhizoxin and phomopsin A binding.

Dolastatin 10, a cytostatic peptide containing several unique amino acid subunits, was isolated from the marine shell-less mollusk Dolabella auricularia. It inhibits microtubule assembly at concentrations below 5.0 microM (IC50, 3.0 microM) and causes formation of tubulin aggregates at higher (> 10 microM) concentrations in a somewhat different manner from that caused by vinblastine. Electron microscopical analysis showed irregular aggregates of microtubule proteins in the presence of 10 microM dolastatin 10. Dolastatin 10 inhibited the binding of both radiolabeled rhizoxin and phomopsin A to tubulin with inhibition constants (Ki) of 7 x 10(-8) M and 1 x 10(-7) M, respectively. The results suggest that at least one of the binding sites of dolastatin 10 on tubulin is the rhizoxin binding site.

Animals↗

Reduction of brain phosphocreatine in bipolar II disorder detected by phosphorus-31 magnetic resonance spectroscopy.

Brain phosphorus metabolism was measured by 31P-MRS in 15 patients with bipolar II disorder (BP II) and 14 patients with bipolar I disorder (BP I). Phosphocreatine (PCr)levels were significantly lower in patients with BP II in all three psychiatric states compared to 59 normal controls (PCr (%) was 13.5 +/- 1.5 (mean +/- SD) for controls, and 12.2 +/- 1.7, 12.1 +/- 1.3, 12.0 +/- 1.9 for hypomanic, euthymic and depressed bipolar II patients respectively). High values of phosphomonoester (PME) were found in BP II patients in the hypomanic and depressive states, but PME values in the euthymic state did not differ significantly from controls. Intracellular pH of BP II patients in all three psychiatric phases was similar to control values, whereas euthymic BP I patients had lower pH values. These results suggest that brain high energy phosphate metabolism may be impaired in BP II and that there may be pathophysiological differences between BP I and BP II.

Adenosine Triphosphate↗

Correlations of phosphomonoesters measured by phosphorus-31 magnetic resonance spectroscopy in the frontal lobes and negative symptoms in schizophrenia.

Frontal lobe dysfunction has been linked to negative symptoms of schizophrenia. We used phosphorus-31 magnetic resonance spectroscopy (31P-MRS) to examine phosphorous metabolism in frontal brain regions in 26 schizophrenic patients compared with 26 sex- and age-matched control subjects. The relative signal intensities of phosphorous metabolites in frontal regions did not differ significantly between schizophrenic patients and control subjects. However, phosphomonoester levels were significantly decreased in frontal regions of 12 schizophrenic patients who had high scores on negative symptom subscales from the Brief Psychiatric Rating Scale (i.e., emotional withdrawal, motor retardation, and blunted affect) compared with 14 patients with low negative symptom scores on the same subscales and control subjects. The correlations between negative symptoms and phosphorous metabolism in the frontal lobes support the "hypofrontality hypothesis" in schizophrenia.

Adenosine Triphosphate↗

Phosphorus-31 magnetic resonance spectroscopy and ventricular enlargement in bipolar disorder.

Phosphorus-31 magnetic resonance spectroscopy (31P-MRS) was used to examine whether reduced levels of phosphomonoesters (PME) were correlated with ventricular enlargement in 40 patients with bipolar disorder and 60 age-matched normal control subjects. Ventricular enlargement was assessed by magnetic resonance imaging (1H-MRI) using the following three methods: Evans ratio (ER), Huckman number (HN), and minimum distance of caudate nuclei (MDCN). Although MDCN and ER were significantly larger in the patient group, no significant correlations were found between 31P-MRS and 1H-MRI. PME was negatively correlated with age in bipolar disorder. Decreased levels of PME were found only in bipolar I disorder. Intracellular pH was positively correlated with duration of lithium treatment. These results suggest that the observed PME reduction was not related to ventricular enlargement, but the issue should be further studied with volumetric MRI analysis.

Adult↗