[Pros and cons of telling patients their diagnosis].
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Diagnosis↗
Biomedical subjects
H Terada
Publications and source records attributed to H Terada.
Characterization of cysteine residues of mitochondrial ADP/ATP carrier with the SH-reagents eosin 5-maleimide and N-ethylmaleimide.
The effects of the membrane-impermeable fluorescent sulfhydryl reagent eosin 5-maleimide (EMA) and the membrane-permeable sulfhydryl reagent N-ethylmaleimide (NEM) on ADP transport via the ADP/ATP carrier and their labeling sites in the carrier were studied in bovine heart submitochondrial particles. Of the 4 cysteine residues in the carrier, EMA labeled Cys159 very rapidly, Cys56 slowly, and Cys256 very slowly and did not label Cys128. Its labeling of Cys159 was associated with inhibition of the ADP transport, suggesting that the peptide segment containing Cys159 is involved in the transport of adenine nucleotides. In contrast to the very rapid binding of EMA to Cys159, NEM bound to Cys56 more slowly and labeled Cys159 and Cys256 much more slowly. Like EMA, it did not react with Cys128. The labeling of Cys56 with NEM also inhibited ADP transport. From these results, the locations of these cysteine residues in the ADP/ATP carrier are discussed in relation to the transport of adenine nucleotides mediated by the ADP/ATP carrier.
Animals↗
Isolation and characterization of cDNA clones and a genomic clone encoding rat mitochondrial adenine nucleotide translocator.
Two cDNA clones encoding rat mitochondrial adenine nucleotide translocator were isolated from libraries constructed from mRNAs of heart and liver. These two clones corresponded to the heart-skeletal muscle type (ANT1) and fibroblast type (ANT2), respectively. A genomic clone encoding rat ANT1 was also isolated and characterized.
Amino Acid Sequence↗
Evolution of the type II hexokinase gene by duplication and fusion of the glucokinase gene with conservation of its organization.
The type I, II, and III isozymes of mammalian hexokinase (100 kDa) all consist of a duplicated, highly homologous peptide sequence, each half of which is very similar to that of glucokinase (type IV hexokinase, 50 kDa) and yeast hexokinase (50 kDa). We isolated a genomic clone of type II hexokinase that contained five exons encoding the C-terminal region of type II hexokinase. The positions of intron insertions of the isolated clone were found to be identical with those of the glucokinase gene, indicating that the type II hexokinase gene arose from the glucokinase gene. Furthermore, we prepared two DNA fragments of the type II hexokinase gene amplified from total genomic DNA. The exons in these fragments were found to be constructed by linkage of the coding region of the last exon and second exon of the glucokinase gene, indicating that the hexokinase gene arose by fusion of two glucokinase genes. These results clearly show that the mammalian hexokinase gene evolved from the glucokinase gene by gene duplication and fusion with conservation of the gene organization.
Amino Acid Sequence↗
The lipophilic weak base (Z)-5-methyl-2-[2-(1-naphthyl)ethenyl]-4-piperidinopyridine (AU-1421) is a potent protonophore type cationic uncoupler of oxidative phosphorylation in mitochondria.
The lipophilic weak base AU-1421 acts as a simple protonophoric uncoupler of oxidative phosphorylation in rat liver mitochondria judging from the following observations. In the absence of any carrier lipophilic anions or P(i), AU-1421 stimulated the rate of state 4 respiration maximally about 7-fold at a concentration of 30 nmol/mg mitochondrial protein. At the same maximum effective concentration, it also inhibited ATP synthesis, released oligomycin-inhibited state 3 respiration, dissipated the proton motive force in the energized state, and activated latent H(+)-ATPase. AU-1421 also allowed proton conduction in both mitochondrial membranes and liposomes. These actions of AU-1421 resemble those of the typical anionic uncoupler SF6847. A marked difference between the two was, however, that ATPase activation by AU-1421 was not suppressed at higher concentrations of AU-1421, whereas ATPase activated by SF6847 was suppressed on increase of the SF6847 concentration. The finding that this simple protonophoric cation acts as an uncoupler at a micromolar concentration is significant, because all true (i.e., protonophore type) uncouplers known so far are anionic not cationic. Thus, AU-1421 is a unique uncoupler of the protonophore type.
Adenosine Triphosphate↗
Phase IV group study of natural human interferon alpha (HLBI) on chronic myelogeneous leukaemia.
Under the control of Kanagawa CML/HLBI phase IV study group in Japan, 18 cases out of registered 30 cases of chronic myelogeneous leukaemia consisting of 17 chronic phase and 1 accelerated phase, during July, 1991 to January, 1992, were analyzed for their hematological responses and cytogentic responses preliminarily. Hematological response rate (PR + CR) was 83.3% including 50.0% of CR, as judged by Kimura's criteria after treatment with HLBI alone (16 cases) or/and with other chemotherapy (2 cases). The dosage and duration of HLBI therapy required to get into the complete remission ranged from 212 to 1272 millions IU and between 6 to 42 weeks (mean value was 20 weeks), respectively. The clonally proliferated leukocytes and decreased physiological hematopoiesis started to recover from 2 to 4 weeks and reached their normal ranges from 16 weeks after 6 millions IU of HLBI were administered every day. In the 4 cases examined, 3 cases showed minimal cytogenetic responses and a case showed no cytogenetic response. Slight and temporary adverse effects were observed in 15 out of 18 cases (83.3%) including fever, general malaise, appetite loss, eruption, diarrhea, glossitis, hypogustation, weight loss and local muscle pain.
Adult↗
Spermine accelerates iron-induced lipid peroxidation in mitochondria by modification of membrane surface charge.
The polyamine spermine was found to make the mitochondrial membrane more susceptible to lipid peroxidation induced by adenosine 5'-diphosphate (ADP)/Fe2+. It shortened the lag time before induction of peroxidation, but did not affect the rate of lipid peroxidation. It had no effect on lipid peroxidation of electrically neutral egg yolk phosphatidylcholine liposomes, but had an effect on lipid peroxidation of negatively charged liposomes consisting of egg yolk phosphatidylcholine and bovine heart cardiolipin similar to that on peroxidation in mitochondria. Spermine decreased the negative zeta-potential of these negatively charged liposomes consisting of phosphatidylcholine and cardiolipin. These results suggest that the hydrophilic polycation spermine reduces the negative charge on the surface of mitochondrial membrane, possibly by its interaction with negatively charged polar heads of phospholipids, and that this neutralization of the surface charge renders the mitochondrial membrane more susceptible to induction of lipid peroxidation induced by ADP/Fe2+.
Adenosine Diphosphate↗
Antitumor agents, 138. Rotenoids and isoflavones as cytotoxic constitutents from Amorpha fruticosa.
Eight cytotoxic compounds have been isolated from the CHCl3 extract of Amorpha fruticosa. One compound, 6'-O-D-beta-glucopyranosyldalpanol [10], is a new cytotoxic rotenoid. Another known rotenoid, 12 alpha beta-hydroxyamorphigenin [6], was first shown to exhibit extremely potent cytotoxicity (ED50 < 0.001 microgram/ml) in six neoplastic cell lines. In addition to these compounds, three isoflavones (afrormosin [1], 7,2',4', 5'-tetramethoxyisoflavone [2], 8-methylretusin [3]) and five rotenoids (amorphispironone [4], amorphigenin [5], dalpanol [7], 12a beta-hydroxydalpanol [8], and tephrosin [9]) were isolated. Compound 8 was isolated for the first time as a natural product from this plant. The structures of these compounds were established on the basis of spectral data; some were further confirmed by X-ray crystallographic analysis.
Antineoplastic Agents, Phytogenic↗
Studies on inhibitors of skin tumor promotion, XII. Rotenoids from Amorpha fruticosa.
As a part of screening studies for chemopreventive agents (anti-tumor-promoters), six North American plants belonging to the Amorpha genus were tested using an in vitro assay system. Of these plants, Amorpha fruticosa exhibited strong inhibitory effects on Epstein-Barr virus early antigen (EBA-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Also six rotenoids, amorphispironone [1], tephrosin [2], amorphigenin [3], 12a-hydroxyamorphigenin [4], 12a-hydroxydalpanol [5], and 6'-O-D-glucopyranosyldalpanol [6], were isolated from the leaves of A. fruticosa. Among these retenoids, 1 and 2 exhibited remarkable inhibitory effects of EBV-EA activation induced by TPA. Further, 1 and 2 exhibited significant anti-tumor-promotion effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. These investigations suggested that these rotenoids might be valuable anti-tumor-promoters.
9,10-Dimethyl-1,2-benzanthracene↗
Image sharpness and contrast transfer in coherent confocal microscopy.
Confocal microscopes provide clear, thin optical sections with little disturbance from regions of the specimen that are not in focus. In addition, they appear to provide somewhat greater lateral and axial image resolution than with non-confocal microscope optics. To address the question of resolution and contrast transfer of light microscopes, a new test slide that enables the direct measurement of the contrast transfer characteristics (CTC) of microscope optics at the highest numerical aperature has been developed. With this new test slide, the performance of a confocal scanning laser microscope operating in the confocal reflection mode and the non-confocal transmission mode was examined. The CTC curves show that the confocal instrument maintains exceptionally high contrast (up to twice that with non-confocal optics) as the dimension of the object approaches the diffraction limit of resolution; at these dimensions, image detail is lost with non-confocal microscopes owing to a progressive loss of image contrast. Furthermore, we have calculated theoretical CTC curves by modelling the confocal and non-confocal imaging modes using discrete Fourier analysis. The close agreement between the theoretical and experimental CTC curves supports the earlier prediction that the coherent confocal and the incoherent non-confocal imaging mode have the same limit of resolution (defined here as the inverse of the spatial frequency at which the contrast transfer converges to zero). The apparently greater image resolution of the coherent confocal optics is a consequence of the improved contrast transfer at spacings which are close to the resolution limit.
Diatoms↗
Supraophthalmic chemotherapy with long tapered catheter: distribution evaluated with intraarterial and intravenous Tc-99m HMPAO.
Supraophthalmic intraarterial chemotherapy has not become popular due to a high incidence of damage to the normal brain and eye. This damage is due to inhomogeneous distribution of the agent secondary to streaming and other flow-related phenomena. To try to minimize this complication, the authors developed a catheter and studied different infusion techniques. A 4.5-F catheter tapered to 2.5 F was used to perform supraophthalmic intraarterial chemotherapy in 26 patients with malignant gliomas. Forty-one of 45 catheterizations were successful. In 17 patients (20 procedures), technetium-99m hexamethyl-propyleneamine oxime (HMPAO) was then injected through the catheter and single photon emission computed tomography was performed to assess the cerebral distribution of the radiopharmaceutical with either a pulsatile or continuous infusion technique. Diffuse and relatively homogeneous distribution of Tc-99m HMPAO was observed with fast pulsatile infusion (10 of 10 procedures); however, inhomogeneous distribution was mostly seen with slow continuous infusion (eight of 10 procedures).
Adolescent↗
Fibulo-tibial weight index--a new criterion for sex identification based on the lower leg bones.
This study was designed in an attempt to determine whether the fibula can provide reliable information for sexing human bones, if measurements include tibial indices. Our results allow us to introduce a new criterion for sexing long bones: the fibulo-tibial weight index. Bone weight was determined, together with conventional measurements, such as maximum bone length and mid-shaft circumference. The materials consisted of dried tibiae and fibulae of 71 recently decreased Japanese males and 31 females. The mean value of the fibulo-tibial weight index was very significantly greater in females than in males. In discriminant analysis, the rate of correct sex discrimination was improved by the inclusion of the fibulo-tibial weight index.
Discriminant Analysis↗
Characteristic bleaching profiles of cyanine dyes depending on active oxygen species in the controlled Fenton reaction.
The bleaching of cyanine-type pentamethine trinuclear dyes by active oxygen species (AOS), superoxide and hydroxyl radical, were studied under the xanthine-xanthine oxidase system and the Fenton reaction, respectively. The gradual bleaching of dyes occurred as the result of superoxide produced in the xanthine-xanthine oxidase system. However, the bleaching of cyanine dyes by Fenton reagent varied depending on the reaction conditions. If a normal Fenton reaction of Fe(II) and hydrogen peroxide (H2O2) took place, a hydroxyl radical was generated instantly. A Fenton reaction with an excess of [H2O2] over [Fe(II)] resulted in a gradual bleaching of the dye initiated by the hydroxyl radical, Fe(III) and H2O2. In this reaction, cyanine dyes with shorter side chains were bleached faster than those with longer ones. We controlled the Fenton reaction condition (Fe(II) or Fe(IIO)/H2O2 at pH 3.5 in the dark) to generate a specific AOS such as a hydroxyl radical (.OH) or superoxide (.O2-). Studies using xanthine-xanthine oxidase (pH 7.8), the Fe(II)-dipyridyl complex and various scavengers such as superoxide dismutase (SOD) and hyaluronic acid, revealed that .O2- was the primary radical responsible for this controlled Fenton reaction. This finding shows that this controlled Fenton reaction would be an effective AOS generation method, and that cyanine dyes may be hopeful probes for the detection of AOS.
Coloring Agents↗
Effect of inorganic phosphate on iron-induced lipid peroxidation in rat liver mitochondria.
The effect of inorganic orthophosphate (Pi) on iron-induced lipid peroxidation in non-respiring rat liver mitochondria was studied and compared with that of adenosine 5'-diphosphate (ADP) at pH 7.4. Under the experimental conditions used, lipid peroxidation was induced by Fe2+ in conjunction with Pi and/or ADP, but not by Fe2+ alone. The characteristics of Fe(2+)-induced lipid peroxidation supported by Pi and by ADP were different: ADP-supported peroxidation took place after a lag-time and proceeded until all the O2 in the incubation medium was consumed, whereas the Pi-supported peroxidation exhibited a longer lag-time and a higher rate, but stopped when half the O2 was consumed. These features were ascribed to the fact that Pi forms active iron-oxygen complexes more rapidly than ADP, but the lifetimes of these complexes are less than those of the complexes with ADP. Furthermore, the ability of Pi to form active iron-oxygen complexes was found to be less than that of ADP. Fe2+, in conjunction with Pi and/or ADP, was found to induce lipid peroxidation in respiring mitochondria, although to a lesser extent than in non-respiring mitochondria.
Adenosine Diphosphate↗
Effects of phospholipase C on action potentials and intracellular Ca2+ concentration in guinea pig heart.
To clarify the role of phospholipase C (PLC) in arrythmias and cell injury during myocardial ischemia/reperfusion, we studied its effects on electrophysiology and [Ca2+]i in guinea pig hearts. After exposure to PLC (1 and 2 U/ml), the action potential durations of right ventricular papillary muscles were decreased. Delayed afterdepolarizations were observed in all of the preparations, and some developed into triggered activities. Developed tension decreased after an initial increase for the first 5 min, while resting tension increased consistently. The effects of PLC (0.02, 0.1, and 0.2 U/ml) on [Ca2+]i of ventricular myocytes were measured using fura-2 fluorescence. The ratio of rod-shaped cells to all cells decreased in a time- and a concentration-dependent manner. Perfusion with 0.1 U/ml PLC elevated [Ca2+]i from 56 +/- 5 nM to 245 +/- 47 nM before cell rounding, and to 1167 +/- 172 nM after cell rounding, suggesting that PLC causes Ca2+ overload. In conclusion, activation of PLC may play a role in arrhythmias and cell injury during ischemia/reperfusion. The increase in [Ca2+]i during ischemia/reperfusion may activate phospholipase, which would further increase [Ca2+]i to form a vicious cycle.
Action Potentials↗
Ca2+ transients and cell shortening in diabetic rat ventricular myocytes.
To investigate the role of abnormal Ca2+ metabolism in the diminished contractile function of diabetic myocardium, we measured the Ca2+ transients and cell contraction of diabetic rat myocytes. Isolated diabetic (8 weeks after 40 mg/kg streptozotocin, i.v.) and normal myocytes were loaded with acetoxymethyl ester of indo-1 (indo-1/AM). Ca2+ transients and cell circumferential shortening were measured simultaneously, using high temporal resolution video image analysis. The diastolic base and systolic peak of Ca2+ transients were significantly lower in diabetic myocytes than in normal myocytes (peak ratios: 0.49 +/- 0.02 vs 0.56 +/- 0.01, p < 0.05; base ratios: 0.43 +/- 0.01 vs 0.48 +/- 0.01, p < 0.01, Mean +/- SE). The cell circumferential shortening of diabetic myocytes was also significantly lower than that of normal myocytes (2.9 +/- 0.3% vs 5.2 +/- 0.9%, p < 0.05). Although isoproterenol (10(-8) and 10(-7) M) increased the peak of Ca2+ transients in both diabetic and normal myocytes, the peak value of Ca2+ transients in the diabetic group was significantly lower than that in the normal group. The decreased Ca2+ transients may be responsible for the decreased contractile function in diabetic myocardium.
Animals↗
[Acetazolamide effect on vascular response in crossed cerebellar diaschisis as measured by 99mTc-HMPAO SPECT].
We studied the effect of acetazolamine (DIAMOXR) on vascular response in areas with crossed cerebellar diaschisis (CCD) using consecutive 99mTc-hexamethyl-propyleneamine oxime (HMPAO) SPECT studies before and after DIAMOX administration with a subtraction method. Regions of interest were drawn over the bilateral cerebellar cortices and interhemispheric asymmetry indices (IAI) were obtained. Eleven of 14 patients with CCD at baseline showed decrease of IAI after DIAMOX administration. Although there is a possibility of underestimation of increase in perfusion in unaffected cerebellar hemisphere, this result suggests a greater increase in perfusion in the affected cerebellar hemisphere as compared with in the contralateral unaffected one and suggests more dilatation of the arterioles in areas with CCD post-DIAMOX than in areas without CCD. However nonsignificant correlation between IAI at baseline and difference of IAI from baseline to post-DIAMOX did not support the hypothesis of more dilatation post-DIAMOX of more constricted arterioles.
Acetazolamide↗
[CT diagnosis of cerebral infarction].
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Cerebral Infarction↗