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Biomedical subjects

T Saijo

Publications and source records attributed to T Saijo.

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

Demonstration of an unstable variant of pyruvate dehydrogenase protein (E1) in cultured fibroblasts from a patient with congenital lactic acidemia.

The deficiency of pyruvate dehydrogenase enzyme complex causes congenital lactic acidemia and devastating neurologic abnormalities in newborns and children. In the majority of cases, the basic defect appears to be in the pyruvate dehydrogenase (E1) component, which consists of two subunits, alpha and beta. Whereas some patients are deficient of a single subunit, in other patients both subunits of E1 are missing. To find out why two proteins were deficient, we investigated the cultured fibroblasts of a female patient who had missing E1-alpha and E1-beta protein bands on Western blot. Radiolabeling-immunoprecipitation studies with 35S-methionine revealed that patient fibroblasts synthesized normal sized precursor E1-alpha and E1-beta proteins, which were presumably transported into mitochondria and processed into normal sized mature proteins. However, pulse-chase analysis showed that alpha- and beta-proteins were degraded rapidly compared to normal. Our findings proved that alpha- and beta-subunits were synthesized and processed normally but failed to form a stable structure for incorporation into the pyruvate dehydrogenase complex.

Cells, Cultured↗
PubMed1991

Hemifacial spasm caused by a spontaneous dissecting aneurysm of the vertebral artery. Case report.

The authors describe the first reported case of dissecting aneurysm presenting with hemifacial spasm. The patient was a 58-year-old woman with left hemifacial spasm of 2 years' duration. Cranial nerve examination was otherwise normal and no other clinical symptoms were observed. Vertebral angiography revealed a fusiform enlargement of the left vertebral artery and contrast medium remaining in the intramural false lumen in the venous phase. Microvascular decompression of the facial nerve with wrapping of the aneurysm resulted in complete relief of the hemifacial spasm.

Aortic Dissection↗
PubMed1991

A unique mutation in the vitamin D receptor gene in three Japanese patients with vitamin D-dependent rickets type II: utility of single-strand conformation polymorphism analysis for heterozygous carrier detection.

Vitamin D-dependent rickets type II is a hereditary disease resulting from a defective vitamin D receptor. In three Japanese patients with vitamin D-dependent rickets type II whose fibroblasts displayed normal cytosol binding and impaired nuclear uptake of 1,25-dihydroxyvitamin D3, western, Southern, and northern analyses failed to disclose any abnormalities in vitamin D3 receptor protein and its gene. Exons 2 and 3 of the vitamin D receptor cDNA, which encode the DNA-binding domain consisting of two zinc fingers, were amplified by PCR and sequenced to identify the specific mutations in the vitamin D receptor gene. In the three patients and one normal control a T-to-C transition was found in the putative initiation codon, while this transition was not observed in another normal control. This finding suggested that an original initiation codon was located at positions 10-12 in the human vitamin D receptor cDNA sequence reported previously. In contrast, a unique G-to-A transition at position 140 in exon 3, resulting in substitution of arginine by glutamine at residue 47, was revealed only in these three patients. The arginine at 47 is located between two zinc fingers and is conserved within all steroid hormone receptors. Therefore, it is highly conceivable that this amino acid substitution is responsible for the defect of the vitamin D receptor in the patients. Single-strand conformation polymorphism analysis of amplified DNA confirmed that all patients were homozygous and that parents from one family were heterozygous carriers for this mutation.

Amino Acid Sequence↗
PubMed1991

[A case with MELAS associated with epilepsia partialis continua].

We report a 14-year-old boy with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS) who presented repeated episodes of abdominal pain and vomiting since the age of 8 years. In addition, he developed strokelike episodes with myoclonic seizures and transient hemiplegia on three occasions. At the age of 14-1/12-years, he also developed epilepsia partialis continua persisting for 10 days, which was associated with myoclonic seizures synchronized with spike discharges at the right central area. Laboratory examination disclosed increased levels of lactate and pyruvate in serum and CSF and low density areas in the bilateral temporal regions on CT scan. Muscle biopsy showed scattered ragged-red fibers. The enzyme activities (pyruvate dehydrogenase complex, pyruvate carboxylase, phosphoenol pyruvate carboxykinase, and cytochrome c oxidase) and the rates of decarboxylation of [3-14C]pyruvate in cultured skin fibroblasts were within normal ranges.

Acidosis, Lactic↗
PubMed1990

Effect of long-term treatment with massive doses of 1 alpha-hydroxyvitamin D3 on calcium-phosphate balance in patients with vitamin D-dependent rickets type II.

Three patients with vitamin D-dependent rickets type II were given massive doses of 1 alpha-hydroxyvitamin D3 for 29 to 36 months and their calcium-phosphate balance was studied during treatment and one month after cessation of treatment. During treatment fasting hypercalciuria was observed in patient 1 and an increased rate of calcium excretion after calcium loading in patients 1 and 2. In these patients, calcium excretion was parallel with the serum 24,25-dihydroxyvitamin D concentration, which may reflect the level of receptor for 1,25-dihydroxyvitamin D. These findings suggested that the responsiveness to 1,25-dihydroxyvitamin D improved during long-term treatment of these two patients with vitamin D-dependent rickets type II.

Calcium↗
PubMed1990

25-Hydroxyvitamin D-24-hydroxylase in phytohemagglutinin-stimulated lymphocytes: intermediate bioresponse to 1,25-dihydroxyvitamin D3 of cells from parents of patients with vitamin D-dependent rickets type II.

A method for assay of 25-hydroxyvitamin D-24-hydroxylase (24-hydroxylase) activity in phytohemagglutinin (PHA)-stimulated lymphocytes was applied to determine whether vitamin D-dependent rickets type II (VDDR II) is hereditary. In normal lymphocytes incubated with PHA for 3 days, maximal and half-maximal responses of 24-hydroxylase were observed after exposure to 10(-8) mol/L and (1.3 +/- 0.4) x 10(-9) mol/L 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], respectively. These responses were similar to those of cultured skin fibroblasts. In contrast, after exposure to 10(-8), 10(-7), and 10(-6) mol/L 1,25-(OH)2D3, no 24-hydroxylase activity was detected in cells from patients with VDDR II, and intermediate activity was observed in cells from their parents. These findings indicated the presence of an intracellular receptor-effector system for 1,25-(OH)2D3 in peripheral lymphocytes. Heterozygotes of VDDR II could be identified, and autosomal recessive inheritance of the disease was demonstrated. Detection of heterozygotes of this disease was not possible by assay of inhibition of thymidine incorporation, another marker of the function of 1,25-(OH)2D3 in PHA-stimulated lymphocytes. Therefore, assay of 24-hydroxylase induction reflected the receptor status more closely than assay of inhibition of DNA biosynthesis. The assay of 24-hydroxylase activity in PHA-stimulated lymphocytes described here will be useful for diagnosis of VDDR II and study of families of patients with this disease.

24,25-Dihydroxyvitamin D 3↗
PubMed1989

Inhibitory effects of methyl 7-butyl-4,5,6,7-tetrahydro-3-methylamino-4,6-dioxo-5-propyl- 2H-pyrazolo[3,4-d]pyrimidine-2-carboxylate (AA-2379) on lysosomal enzyme and arachidonic acid release from rat polymorphonuclear leukocytes and its mode of action.

AA-2379 (methyl 7-butyl-4,5,6,7-tetrahydro-3-methylamino-4,6-dioxo-5-propyl- 2H-pyrazolo [3,4-d]pyrimidine-2-carboxylate) has antiinflammatory, analgesic, and antipyretic activities, and inhibits the type III allergic (Arthus) reaction. In the studies reported here, we investigated the effect of AA-2379 on rat polymorphonuclear leukocyte (PMN) functions to clarify the mechanism of the antiinflammatory and antiallergic actions of AA-2379. AA-2379 at 10(-4) M inhibited lysozomal enzyme release. AA-2379 inhibits formyl methionyl-leucyl-phenylalanine (fMLP)- and C5a-induced arachidonic acid release; their 50% inhibitory concentrations were 2.8 x 10(-5) and 3.8 x 10(-5) M, respectively. Because dibutyryl cAMP, a cAMP analogue, and 3-isobutyl-1-methylxanthine, a cAMP phosphodiesterase inhibitor, inhibited fMLP-induced arachidonic acid release, and AA-2379 inhibited cAMP phosphodiesterase and increased cAMP content in PMNs, it is likely that AA-2379 inhibited arachidonic acid release by increasing cAMP content in rat PMNs. Furthermore, from the studies of fMLP-induced arachidonic acid release in Ca free medium it is suggested that AA-2379 inhibits the process which depends on Ca concentration in the medium. These results suggest that the inhibitory effect of AA-2379 on inflammation and allergic reactions such as the Arthus reaction is partly exerted by inhibiting PMN functions such as arachidonic acid and lysozomal enzyme release.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1989

Effect of sodium dichloroacetate on human pyruvate metabolism.

Sodium dichloroacetate (DCA) was administered orally at doses of 12.5 to 50 mg/kg body weight twice or three times per day to a patient with mitochondrial encephalomyopathy associated with congenital lactic acidemia. During therapy, the rates of decarboxylation of (1-14C) pyruvate and (3-14C) pyruvate, which represent the activity of the pyruvate dehydrogenase (PDH) complex and the function of the TCA cycle, respectively, were markedly increased in the platelets and increases in the lactate levels in the blood and urine during exercise were markedly reduced. These results suggest that oral administration of DCA causes significant increases in the activities of the PDH complex and TCA cycle not only in the platelets but also in various tissues of humans, which is important as a pathway for production of energy, resulting in decreases in the lactate and pyruvate levels in the blood and cerebrospinal fluid.

Acetates↗
PubMed1988

Inhibitory effect of methyl 7-butyl-4,5,6,7-tetrahydro-3-methylamino-4,6-dioxo-5-propyl-2H-pyrazol o[3, 4-d]pyrimidine-2-carboxylate (AA-2379) on type III allergic (Arthus) reaction.

Methyl 7-butyl-4,5,6,7-tetrahydro-3-methylamino-4,6-dioxo-5-propyl-2H- pyrazolo[3,4-d]pyrimidine-2-carboxylate (AA-2379), a non-steroidal, non-acidic agent, markedly inhibits type III allergic (Arthus) reaction; the ID50 values of AA-2379 in the rat reversed passive Arthus pleurisy, the rat active Arthus pleurisy, and the reversed passive Arthus reaction in rat skin were 5-10 mg/kg, p.o., and 30 mg/kg of AA-2379 inhibited the active Arthus reaction in rabbit skin by about 50%. Dexamethasone, but not acidic non-steroidal anti-inflammatory drugs and aminopyrine, inhibited the Arthus reaction. The vascular permeability in the reversed passive Arthus pleurisy is enhanced biphasically in the early response mediated by physiologically active amines, prostaglandins, and leukotrienes, and in the late response mediated by complements and polymorphonuclear leukocytes (PMNs). AA-2379 inhibited the late response more potently than the early one. Furthermore, when given after the early response was reduced, AA-2379 obviously inhibited the late response. Rat zymosan-induced paw edema and mouse zymosan-activated serum-induced peritonitis, mediated by complements, were dose-dependently inhibited by AA-2379; the ID50 values were 11.4 and 10.2 mg/kg, p.o., respectively. The results suggest that AA-2379 differs from non-steroidal anti-inflammatory agents in strongly inhibiting the late response of the Arthus reaction, which associated with PMNs.

Animals↗
PubMed1988

Antiinflammatory, analgesic, and antipyretic activities of methyl 7-butyl-4,5,6,7-tetrahydro-3-methylamino-4,6-dioxo-5-propyl-2H-pyrazol o[3, 4-d]pyrimidine-2-carboxylate (AA-2379), a novel non-acidic agent.

The antiinflammatory, analgesic, and antipyretic activities of methyl 7-butyl-4,5,6,7-tetrahydro-3-methylamino-4,6-dioxo-5-propyl-2H-pyrazolo[ 3, 4-d]pyrimidine-2-carboxylate (AA-2379), a novel non-acidic agent, were examined. 1. AA-2379 had a potent antiinflammatory activity; 3-25 mg/kg, p.o. of the compound inhibited rat carrageenin-, bradykinin-, trypsin-, formalin-, dextran-, and nystatin-induced paw edema; mouse traumatic edema; and rat croton oil pouch inflammation by about 30%. The compound at 25-50 mg/kg, p.o. also inhibited the vascular permeability induced by histamine, serotonin, and bradykinin. 2. AA-2379 had an analgesic activity; the ID50 values in mouse phenylquinone-induced writhing were 10.1 mg/kg, p.o. and the compound at 12.5 mg/kg, p.o. inhibited dog urate arthritis. 3. AA-2379 at 3-10 mg/kg, p.o. showed antipyretic activity in febrile rats and rabbits. 4. AA-2379, at 500 mg/kg, p.o. was not ulcerogenic in rats. 5. These data show that AA-2379 is more active than non-acidic antiinflammatory agents, such as tiaramide and aminopyrine.

Animals↗
PubMed1987

Mechanism of action of an antiallergic agent, amlexanox (AA-673), in inhibiting histamine release from mast cells. Acceleration of cAMP generation and inhibition of phosphodiesterase.

Amlexanox markedly inhibits histamine release from rat mast cells. To clarify the mechanism of this inhibition, we investigated the effect of amlexanox on cAMP content, which, when increased, inhibits histamine release in rat peritoneal mast cells. At concentrations of 10(-8)-10(-6)M, amlexanox or isoproterenol increased the cAMP content of mast cells over that of control cells about 2-fold. When the mast cells were incubated with 10(-8), 10(-7) and 10(-6) M of amlexanox combined with 10(-7) M isoproterenol, the cAMP contents were synergistically increased 15-, 60- and 88-fold, respectively. 3-Isobutyl-1-methylxanthine (IBMX) at 10(-6)-10(-4) M increased the cAMP content 1.7-3.8-fold, and a combination of 10(-4) M IBMX and 10(-7) M isoproterenol synergistically increased the cAMP content 41-fold. A combination of amlexanox and IBMX synergistically increased the cAMP content 19-fold. The increase in cAMP content, when amlexanox and isoproterenol were combined, was transient; it peaked at 0.5 min after the drugs were administered, then decreased to 20-30% of the peak value about 2 min later. Pretreatment of mast cells with amlexanox reduced the effect of the combination of amlexanox and isoproterenol, indicating tachyphylaxis; pretreatment with IBMX had no such effect. The cAMP content of macrophages was also increased by amlexanox, but when combined with isoproterenol or PGE2, the effect was additive. Amlexanox inhibited cAMP phosphodiesterase in rat mast cells; its IC50 value was 1.4 X 10(-5) M, and its inhibitory activity was half that of IBMX.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminopyridines↗
PubMed1987

1 alpha-hydroxyvitamin D3 treatment of three patients with 1,25-dihydroxyvitamin D-receptor-defect rickets and alopecia.

Three patients with clinically different severities of vitamin D-dependent rickets, type II, with alopecia, which is 1,25-dihydroxyvitamin D-receptor-defect rickets and is particularly resistant to treatment with calciferol analogues, were treated with large doses of 1 alpha-hydroxyvitamin D3 (1 alpha-(OH)D3) and 2 g of calcium lactate. Except for the alopecia, all of the abnormalities of patients 1 and 2 were reversed by treatment with 3 micrograms/kg/d of 1 alpha-(OH)D3, and those of patient 3, who had the severest manifestations, were reversed by treatment with 6 micrograms/kg/d. The serum 24,25-dihydroxyvitamin D concentrations of the three patients were low before treatment and those of patients 1 and 2 increased during treatment. These findings suggest that in patients 1 and 2, 25-hydroxyvitamin D-24-hydroxylase was stimulated via a 1,25-dihydroxyvitamin D-receptor-mediated system by treatment with 1 alpha-(OH)D3.

24,25-Dihydroxyvitamin D 3↗
PubMed1987

[Clinical observations on cefuzonam in pediatrics].

Cefuzonam (L-105, CZON) was given intravenously to 20 pediatric patients with the following acute bacterial infections: 13 of bronchopneumonia and 1 each of tonsillitis, purulent cervical lymphadenitis and acute tonsillitis, laryngitis, bronchitis, pyothorax, purulent meningitis complicated with septic arthritis, and urinary tract infection. Good clinical responses were obtained in all of the 20 patients and bacterial eradication of all 16 strains. No side effect was observed except 3 cases of slight elevation of transaminase, and 1 case each of soft stool and eosinophilia. From the above clinical results, it appears that CZON is a useful antibiotic for the treatment of pediatric patients with various kinds of bacterial infections.

Acute Disease↗
PubMed1986

Rapid diagnosis of vitamin D-dependent rickets type II by use of phytohemagglutinin-stimulated lymphocytes.

The interactions of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] with phytohemagglutinin (PHA)-stimulated lymphocytes from normal subjects and three patients with vitamin D-dependent rickets (DDR) type II were investigated. Impaired nuclear uptake and normal cytosol binding of [3H]1,25-(OH)2D3 were observed with PHA-stimulated lymphocytes of these patients as with their cultured skin fibroblasts. Furthermore, the incorporation of [14C]thymidine into PHA-stimulated lymphocytes of the patients was not reduced by 1,25-(OH)2D3, which is known to inhibit proliferation of various cells. These findings suggest that 1,25-(OH)2D3 receptors are reduced or absent in patients with DDR type II. Thus, the capacities of cytosol binding and nuclear uptake of 1,25-(OH)2D3 in PHA-stimulated lymphocytes seem to reflect those of endo-organs such as the intestine and bone. These findings show that a test of the effect of 1,25-(OH)2D3 on thymidine incorporation into PHA-stimulated lymphocytes is useful for rapid diagnosis of DDR type II.

Calcitriol↗
PubMed1986

Role of leukotrienes in rat reversed passive Arthus pleurisy and the effect of AA-861, a 5-lipoxygenase inhibitor.

In studies of the role of leukotrienes in inflammatory reactions, the induction of rat reversed passive Arthus pleurisy (a type III allergic reaction) was employed. Increases of exudate volume, vascular permeability, and migration of inflammatory cells in the pleural cavity were observed. The vascular permeability was enhanced biphasically during 0-30 min (early response) and during 3-6 h (late response) after induction of the pleurisy. The infiltration of inflammatory cells, mainly polymorphonuclear leukocytes, into the cavity increased and reached a maximum 6 h after the pleurisy was induced. Leukotriene B4 (LTB4), 5-monohydroxyeicosatetraenoic acid (5-HETE), and slow-reacting substance of anaphylaxis (SRS-A), consisting of LTC4, LTD4 and LTE4, were detected in the exudate by reversed-phase high-performance liquid chromatography during the early response. The contents of LTC4 reached a maximum 10 min after the challenge, followed by a rapid decrease within 1 h. The rise and decay of LTC4 correlated with the increase in vascular permeability during the early phase. AA-861, a 5-lipoxygenase inhibitor, given intrapleurally inhibited the increase in vascular permeability, cell migration, and generation of leukotrienes during the early phase of the pleurisy. These results indicate that products of the 5-lipoxygenase pathway, such as LTC4 and LTB4, may play an important role as chemical mediators in the inflammatory reaction.

Animals↗