Search PubMed⌕ Search

Biomedical subjects

A Tomoda

Publications and source records attributed to A Tomoda.

At least 55 records · Page 3Linked to original sources
PubMed1991

Progressive myoclonus epilepsy: dentato-rubro-pallido-luysian atrophy (DRPLA) in childhood.

A 22-year-old female with progressive myoclonus epilepsy (PME) considered to be due to hereditary dentato-rubro-pallido-luysian atrophy (DRPLA) was reported. Some of her family members showed progressive myoclonus, seizures, dementia, ataxia and choreoathetosis, with variation of onset from childhood to adult life, which suggested that they had been suffering from DRPLA. CT scan and MRI studies, including some on family members, revealed cerebral and cerebellar atrophy accompanied by dilatation of the fourth ventricle, compatible with the findings in DRPLA reported previously. We emphasize that a detailed family history may be essential in dealing with a PME patient and that DRPLA should be considered in the differential diagnosis of the PME syndrome with onset in childhood, in Japan.

Adolescent↗
PubMed1991

Oxidative condensation of 2-amino-4-methylphenol to dihydrophenoxazinone compound by human hemoglobin.

2-Amino-4-methylphenol was converted to a brownish yellow material by the lysates of human erythrocytes or purified human hemoglobin. The reaction proceeded oxidatively, coupled with the oxidation of hemoglobin. The major component of the brownish yellow material produced by oxidative condensation of 2-amino-4-methylphenol was identified as 3-amino-1,4 alpha-dihydro-4 alpha, 8-dimethyl-2H-phenoxazin-2-one on the basis of its spectral data including NMR spectra, IR spectra, EI mass spectra, and absorption spectra. The changes in 3-amino-1,4 alpha-dihydro-4 alpha,8-dimethyl-2H-phenoxazin-2-one during incubation of purified human hemoglobin and 2-amino-4-methylphenol were analyzed spectrophotometrically and by using HPLC. The reaction mechanism involved may be similar to that of actinomycin synthase, which oxidizes 2-amino-5-methylphenol to the dihydrophenoxazinone.

Cresols↗
PubMed1991

Exonic point mutations in NADH-cytochrome B5 reductase genes of homozygotes for hereditary methemoglobinemia, types I and III: putative mechanisms of tissue-dependent enzyme deficiency.

We analyzed the NADH-cytochrome b5 reductase gene of hereditary methemoglobinemia type I and type III, by using PCR-related techniques. The mutation in type I is a guanine-to-adenine substitution in codon 57 of exon 3 of the NADH-cytochrome b5 reductase gene, and the sense of this codon is changed from arginine to glutamine. In type III the mutation is a thymine-to-cytosine transition in codon 148 of exon 5, causing leucine-to-proline replacement in type III. The former mutation abolishes the MspI recognition site. Homozygosity for the former mutation in a patient with type I was confirmed by restriction analysis of PCR-amplified fragments and by dot blot hybridization of amplified products with allele-specific oligonucleotide probes. The latter mutation generates a recognition site for MspI. Amplification of exon 5 by PCR followed by digestion with MspI revealed homozygosity for this mutation in patients with type-III. Putative mechanisms of tissue-dependent enzyme defects in hereditary methemoglobinemia are discussed.

Adult↗
PubMed1990

Mechanism of coloration of human lenses induced by near-ultraviolet-photo-oxidized 3-hydroxykynurenine.

Tha absorption spectra of human cataractous lenses, classified into four groups on the basis of coloration, were measured by a spectrophotometer equipped with an integrating sphere that is able to detect diffuse reflectance of solid materials. The results revealed that pale-yellow cataractous lenses showed a characteristic absorption spectrum with a peak near 365 nm, coincident with that of 3-hydroxykynurenine, and that brunescent cataractous lenses with high pigmentation showed an absorption spectrum with a peak over 400 nm, coincident with that of xanthommatin, a dimerized compound of 3-hydroxykynurenine. Depending on the coloration of the lens, the position of maximum absorption shifted from 365 to 410 nm and the optical density increased at visible regions. The changes in absorption spectra of pale-yellow lens homogenates were studied in the presence or absence of 3-hydroxykynurenine and by near-ultraviolet (UV) irradiation. Brown pigments were formed in the insoluble proteins of lens homogenates by 48 h of exposition of the samples with 3-hydroxykynurenine to UV irradiation. The absorption spectra of the brown pellets detected by an integrating sphere corresponded well to those of pellets which were obtained from the homogenates of intact human brunescent cataractous lenses. These results strongly suggest that 3-hydroxykynurenine and UV irradiation are involved in the brown pigmentation of human cataractous lenses by formation of xanthommatin.

Amino Acids↗
PubMed1990

Methemoglobinemia with oxidized hemoglobins and modified hemoglobins found in bloods of workers handling aromatic compounds and in those of a man who drank cresol solution.

We found that half-oxidized hemoglobins such as (alpha 2+ beta 3+)2 and (alpha 3+ beta 2+)2, and methemoglobin were significantly increased in the erythrocytes of workers handling chemical compounds in a chemical plant of Japan. In addition, we found two unusual anodic hemoglobins (hemoglobin X and hemoglobin Y) to be present to a large extent in the erythrocytes of the workers investigated (21 persons), using isoelectric focusing electrophoresis on polyacrylamide gel plates. For example, the hemoglobin analysis of a worker showed: hemoglobin X, 6.2%; hemoglobin Y, 26.8%; hemoglobin A + hemoglobin F, 54.5%, half-oxidized hemoglobins, 9.8%; methemoglobin, 1.5%; hemoglobin A2, 2%. Since contents of hemoglobin A decreased by more than 40% of normal levels, and those of oxidized and modified hemoglobins increased up to 40% of total hemoglobins in the erythrocytes of several workers in the plant, we may consider these cases as ones having toxic methemoglobinemia with oxidized and modified hemoglobins. The changes of intracellular hemoglobins in these cases may be due to oxidation and modification of the proteins by chemical compounds absorbed from skin and lungs. Therefore, these hemoglobins may be a good indicator to monitor the health of workers in chemical plants. We also studied the formation mechanism of modified hemoglobins such as hemoglobin X and hemoglobin Y, investigating the reactions of hemoglobin with various aromatic compounds in vitro. On the other hand, we had the opportunity to analyze the changes in oxidized hemoglobins and modified hemoglobins in the blood of a man who drank cresol solution to commit suicide and was sent to a hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

Cresols↗
PubMed1987

Spectroscopic studies of brunescent cataractous lenses.

The absorption spectra of brunescent cataractous lenses and their homogenates were analyzed under various conditions by using a double wavelength spectrophotometer. The absorption spectra of the samples were in good agreement with those of synthetic xanthommatin derived from 3-hydroxykynurenine. The results provided evidence that brown pigment in the brunescent cataractous lenses is mainly composed of xanthommatin.

Amino Acids↗
PubMed1987

Accumulation of inosine 5'-monophosphate in human erythrocytes incubated with inosine.

The changes in inosine 5'-monophosphate (IMP) and adenine nucleotides were studied in human erythrocytes incubated with glucose alone, or with glucose plus inosine in the presence or absence of monoiodoacetate, a strong inhibitor of the glycolytic pathways of the cells. HPLC was useful in analyzing the changes in these nucleotides. When the cells were incubated with glucose and inosine for several hours at pH 7.0, 37 degrees C, they produced much IMP, while the cells incubated with glucose and monoiodoacetate accumulated AMP rapidly within 2 hours, accompanied with the decomposition of ADP and ATP; but IMP was not accumulated. When the cells were incubated with glucose and inosine in the presence of monoiodoacetate, AMP increased more rapidly to about 1400 mu mols/ml of cells within 1 hour and then gradually decreased. ATP was consumed completely and ADP decreased correspondingly. However, IMP was produced in this case, though its accumulation was not so high as in the case with glucose plus inosine without monoiodoacetate. The production of IMP depended on the pH of the cell suspension, i.e., more IMP was produced at higher pHs.

Adenine Nucleotides↗
PubMed1986

Abolishment of inhibitory effects of 3'-deazaadenosine on superoxide generation of guinea pig phagocytes by pre-exposure to phorbol myristate acetate.

Superoxide generation by guinea pig macrophages and polymorphonuclear leukocytes induced by wheat germ agglutinin, immune complexes or formyl-methionyl-leucyl-phenylalanine was inhibited considerably by 3'-deazaadenosine. The pre-exposure of the 3'-dezazaadenosine-treated cells to a small amount of phorbol myristate acetate abolished the inhibitory effect of 3'-deazaadenosine on the generation of superoxide.

Animals↗
PubMed1986

Mechanism of o-aminophenol metabolism in human erythrocytes.

o-Aminophenol was found to be rapidly metabolized to a brown compound in the presence of purified human oxy- and methemoglobin, coupled with the oxidation and reduction of these hemoglobins by o-aminophenol. The final product of o-aminophenol was identified as 2-aminophenoxazine-3-one, by using spectrophotometry and HPLC. The metabolism of o-aminophenol was also observed in human erythrocytes. The production rates of 2-aminophenoxazine-3-one in the cells were very fast, but these were strongly decreased by bubbling carbon monoxide into the cell suspension when intracellular hemoglobin was in the ferrous state. The production of 2-aminophenoxazine-3-one from o-aminophenol in the cells was completely suppressed by cyanide and azide when intracellular hemoglobin was in the ferric state. These results suggest that oxy- and methemoglobin are involved in metabolism of o-aminophenol to 2-aminophenoxazine-3-one in human erythrocytes.

Aminophenols↗
PubMed1986

Effect of triethyltin on enzyme activity in human adult and cord red cells.

Since organotin compounds represent an environmental health hazard, we determined the effect of triethyltin bromide (TTB) on red blood cell (RBC) enzyme activity. TTB produced a concentration-dependent inhibition of hexokinase and pyrimidine 5'-nucleotidase for both adult and cord RBC. D-Glucose, but not ATP or MgCl2, prevented the hexokinase inhibition by TTB. Glucose-6-phosphate dehydrogenase, adenylate kinase, and hypoxanthine-guanine phosphoribosyltransferase were also inhibited by TTB. Cord RBC enzymes were more resistant to the effects of TTB than were adult RBC enzymes. Although TTB is a potent inhibitor of hexokinase, physiologic concentrations of glucose appear to protect the RBC during clinical tin intoxication.

5'-Nucleotidase↗
PubMed1986

Reactions of oxy- and methemoglobin with tryptophan metabolites, 3-hydroxyanthranilic acid and 3-hydroxykynurenine.

It was found that 3-hydroxyanthranilic acid and 3-hydroxykynurenine have the capacity of oxidizing and reducing oxy- and met-hemoglobin. However, tryptophan metabolites such as kynurenine and anthranilic acid in which hydrxyl group is not involved did not oxidize and reduce these hemoglobins. The oxidation of oxyhemoglobin with 3-hydroxyanthranilic acid and 3-hydroxykynurenine was much accelerated in the presence of myo-inositol hexakisphosphate or superoxide dismutase, but was much suppressed in the presence of catalase. Deoxyhemoglobin was not oxidized by these compounds. On the other hand, the reduction of methemoglobin with 3-hydroxyanthranilic acid and 3-hydroxykynurenine proceeded both under aerobic and anaerobic conditions, though the rate of reduction was much faster under aerobic conditions than under anaerobic conditions. The reduction of methemoglobin with these compounds was accelerated by myo-inositol hexakisphosphate, but was partially suppressed by superoxide dismutase under aerobic conditions. On the basis of these results, the paradoxical effects of 3-hydroxyanthranilic acid and 3-hydroxykynurenine are discussed in relation to the mechanism of oxidation and reduction of hemoglobin.

3-Hydroxyanthranilic Acid↗
PubMed1985

Lack of effects of thyroid hormones on human erythrocyte acetylcholine esterase.

Effects of thyroid hormones and their metabolites such as L-T1, L-T2, L-T3 and L-T4 on human erythrocyte acetylcholine esterase were studied. The activity of the enzyme of intact erythrocytes was not affected by these hormones, though studied under various conditions. The physiological significance of the binding of these hormones to erythrocyte membranes remains unclear. Our results indicate that the acetylcholine esterase is not a suitable enzyme for cytochemical bioassay for thyroid hormones.

Acetylcholinesterase↗
PubMed1985

Down-regulation of Fc receptor expression in guinea pig peritoneal exudate macrophages by muramyl dipeptide or lipopolysaccharide.

Expression of Fc receptors on the plasma membrane of guinea pig peritoneal exudate macrophages (PEM) was suppressed to almost one-half of that of the controls by long-term exposure to lipopolysaccharide (LPS) or muramyl dipeptide (MDP) in culture. The effect of the reagents was dose and time dependent, and as little as 0.5 ng/ml LPS or 5 ng/ml MDP was effective for the suppression. The expression of the Fc receptors decreased to 60 to 70% of the control level at 48 hr and to 45 to 50% at 72 hr after incubation of the cells in the presence of LPS or MDP. A Scatchard plot of the binding of 125I-soluble immune complexes (I.C.) to the cells revealed that the decrease in the binding of 125I-I.C. is due to a reduction in the number of Fc receptors on the cell membrane and not to a decreased affinity of the receptors. The membrane protein was radio-labeled with 125I, and the Fc receptors were purified by being bound to insoluble I.C. The specific binding of the 125I-labeled Fc receptors, from the LPS-treated macrophages, to the insoluble I.C. was almost one-half of that from the untreated control cells. SDS-PAGE analysis of the purified 125I-labeled Fc receptors revealed that the major peak of the m.w. 44,000 molecule in the LPS-treated cells was almost one-half of that of the control. Contrary to the effect of LPS or MDP, 72-hr incubation of macrophages with MIF-rich supernatant, cultured from lymph node cells, enhanced the expression of Fc receptors. Macrophages were treated with I.C. for 4 hr at 37 degrees C to remove the Fc receptors from the surface membrane. The reappearance of the receptors on the plasma membrane of the cells was significantly suppressed by LPS and MDP. The effect of LPS on the binding of five murine monoclonal antibodies (Ab) raised against PEM to the macrophage membrane and also that of 125I-wheat germ agglutinin (WGA) or 125I-insulin was studied. The monoclonal Ab were selected for their activity to induce superoxide anion generation in the macrophages, as do I.C., although the binding sites for the monoclonal Ab were not related to Fc receptors. The bindings of the five monoclonal Ab were not affected by exposure of the cells to LPS or MDP. Macrophages treated with the reagents bound as much 125I-insulin or WGA as did the untreated control cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1985

Characterization of three monoclonal antibodies which induce and modulate superoxide anion generation in guinea pig macrophages.

Three monoclonal antibodies (Ab), termed KY 12, KY 22, and KY 25 and raised against guinea pig macrophages, induced superoxide anion (O2-) generation in the cells. Although each monoclonal Ab bound to macrophages, each had a different pattern of binding to other cell types. In response to each of the Ab, the amount of O2- generated by 5 X 10(5) macrophages was between 0.5 and 0.7 nmol/min and was augmented threefold to fivefold by the addition of F(ab')2 fragments of rabbit Abs to mouse Ig. When macrophages were pretreated with soluble immune complexes (I.C.) prior to stimulation by the monoclonal Ab, the O2- generation stimulated by KY 12 or KY 22 was reduced by more than 70%. In contrast, pretreatment of macrophages with I.C. did not reduce O2- generation in response to KY 25. KY 12 and KY 22 stimulated adenyl cyclase activity in macrophages, but KY 25 did not. Pretreatment of the cells with soluble I.C. did not interfere with the enhancing effect of the monoclonal Ab on adenyl cyclase activity. Pretreatment of macrophages with KY 12 reduced by over 60% of subsequent generation of O2- in response to wheat germ agglutinin, I.C., formyl-methionyl-leucyl-phenylalanine, phorbol myristate acetate, KY 22, or KY 25. KY 22 or KY 25 did not suppress the generation of O2- in response to other stimuli. These results suggest that KY 22 and KY 25 activate O2- generation in a manner that differs from that of KY 12. These monoclonal Ab should prove useful in examining the regulation of O2- production.

Adenylyl Cyclases↗
PubMed1985

Fc receptor-mediated desensitization of superoxide (O2-) generation response of guinea-pig macrophages and polymorphonuclear leucocytes.

Guinea-pig macrophages were pretreated with soluble immune complexes (1 hr, at 37 degrees). By this procedure, the capacity of the cells to produce superoxide anions (O2-) upon stimulation with wheatgerm agglutinin (WGA) was inhibited by as much as 80% (desensitization). However, the receptors for WGA were still available on the cell surfaces as determined by the binding of 125I-labelled WGA to both the pretreated and control cells. This inhibition of O2- generation was also observed when opsonized zymosan (Op-zymosan) was used as the stimulus for O2- generation. In contrast, the inhibition by soluble immune complexes was less than 25% of the control levels when the desensitized cells were stimulated with N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) or phorbol myristate acetate (PMA). The same procedure was also used to desensitize guinea-pig polymorphonuclear leucocytes (PMN). In this case, the O2- generation of the PMN was suppressed to 50-55% of the control level when WGA or fMLP was used as stimulus. However, the PMA-induced O2- generation was far less affected by this treatment, as was the case with the macrophages. The activity of the desensitized macrophages for O2- generation recovered gradually to a normal level 24 hr after removal of the immune complexes from the medium. These results suggest that (i) some regulatory mechanisms which suppress the activation of NADPH oxidase are accentuated by prolonged exposure of guinea-pig macrophages and PMN with soluble immune complexes; (ii) the mechanism for O2- generation mediated by WGA or Op-zymosan may be different from that for O2- generation mediated by PMA, and (iii) the mechanism for O2- generation mediated by fMLP differs between macrophages and PMN.

Animals↗
PubMed1985

Hereditary methemoglobinemia due to cytochrome b5 reductase deficiency in blood cells without associated neurologic and mental disorders.

Following the observation of two fraternal patients without neurologic symptoms, but with hereditary methemoglobinemia due to cytochrome b5 reductase deficiency in erythrocytic and nonerythrocytic cells, a familial study of their paternal and maternal relatives was undertaken. Ferrihemoglobin reductase activities in erythrocytes from the two patients were found to be impaired, and cytochrome b5 reductase activities in platelets and leukocytes were essentially absent. Any deficiencies of the enzyme activities seemed not to be found in nonhematopoietic cells. The enzyme activities in blood cells derived from the parents and some of their paternal and maternal family members showed levels intermediate between those of the patients and those of the normal control, which seemed to be heterozygous. The present cases did not belong to either the classic erythrocytic or the generalized type, and their enzyme deficiency was found rather to be restricted to their blood cells and not associated with neurologic and mental disorders. A necessity of diagnosis by tissues other than blood cells is discussed for a severe form of generalized-type hereditary methemoglobinemia with associated neurologic and mental disorders.

Adult↗