Clinical and biochemical phenotype of the MELAS mutation.
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Blotting, Western↗
Biomedical subjects
K Tada
Publications and source records attributed to K Tada.
The molecular defect in propionic acidemia: exon skipping caused by an 8-bp deletion from an intron in the PCCB allele.
Propionic acidemia is an autosomal recessive metabolic disease resulting from a deficiency of propionyl CoA carboxylase (PCC) activity. To investigate the genetic basis of propionic acidemia, we isolated a cDNA encoding the precursor of the beta subunit of human PCC (beta PCC). The cloned cDNA sequence was 1,832 bp long and the open reading frame of 1,617 nucleotides encoded a polypeptide of 539 amino acids with a molecular mass of 58,202 Da. The human beta PCC sequence shared a high degree of homology (91%) with the full-length cDNA of rat beta PCC at the amino acid level; there were only 47 differences among 539 amino acid residues compared. Polymerase chain reaction amplification and sequencing of cDNA from a beta subunit-deficient Japanese patient revealed a deletion of 101 nucleotides consisting of one exon from mature mRNA. This deletion resulted in a frameshift and a stop codon in the new frame. Analysis of the genomic DNA revealed a homozygous 8-bp deletion from bp3 to bp10 of the intron just downstream of the deleted exon. This deletion disrupted the consensus 5' splice signal and led to exon skipping.
Alleles↗
Inhibition of glucose absorption by phlorizin affects intestinal functions in rats.
BACKGROUND: To investigate the mechanism of regulation of intestinal disaccharidase activity and glucose absorption, the effect of dietary intake of phlorizin, a potent and specific inhibitor of intestinal glucose transport, on intestinal disaccharidase activity and Na(+)-dependent glucose transporter was examined in rats. METHODS: Jejunal disaccharidase activity and the number of Na(+)-dependent glucose transporters were determined in rats maintained on a low-starch diet, a high-starch diet, or low-starch diets containing various amounts of phlorizin (0.1%-0.9% wt/wt). RESULTS: Jejunal disaccharidase activity increased in a dose- and time-dependent manner. Stimulation of jejunal disaccharidase activity only occurred when phlorizin was added to starch-containing diets, not when it was added to a carbohydrate-free diet. Addition of the same amount of phloretin and glucose (constituents of phlorizin), to the diet failed to increase disaccharidase activity. The maximum binding of phlorizin to brush border membrane vesicles was increased in the rats fed phlorizin, whereas the dissociation constant remained unchanged, suggesting an increase of glucose transporter expression. CONCLUSIONS: Dietary phlorizin increased the jejunal disaccharidase activity and Na(+)-dependent glucose transporter expression. The trigger for these changes may have been due to an increased luminal glucose content.
Administration, Oral↗
Treatment of residual instability and extensor lag in polydactyly of the thumb.
Extensor indicis tendon transfers were used in six cases with residual deformity of the thumb in polydactyly. The indication was extensor lag and instability of the interphalangeal joint. At mean follow-up of three and a half years, normal stability was improved. Full extension was achieved in three cases and two cases also derived some benefits from this operation. Alignment was improved in five cases.
Child↗
Effect of chronic alcohol intake on rat liver microcirculation assessed by the multiple indicator dilution technique.
To study the hepatic microcirculatory disturbance in alcoholic liver injury, rats were chronically (8-12 weeks) fed with alcohol via a gastric fistula according to the method of Tsukamoto and French (1986). The hepatic microcirculation was studied by measuring the sinusoidal volume (SV) and the apparent space of Disse (DS) volume using a multiple-indicator dilution technique. Both the SV and the DS volume were significantly decreased in the alcohol-fed rats at 8-12 weeks despite the absence of microscopically detectable hepatic fibrosis. Similar changes were noted in the alcohol-fed and control rats regarding expansion of the SV and the DS volume with alterations in portal pressure. However, since the volumes in the alcohol-fed group increased with the increase of portal pressure, they maintained a steady difference from the control values. These results suggested that the decrease of the SV and the DS volume may have been secondary to compression caused by steatosis and/or hepatocyte enlargement, although a possible role for microscopically undetectable hepatic fibrosis could not be ruled out.
Alcoholism↗
Direct evidence for the absence of active Na+ reabsorption in hamster ascending thin limb of Henle's loop.
The mechanisms of Na+ transport across cell membranes were investigated in the in vitro microperfused hamster ascending thin limb (ATL) of Henle's loop using a fluorescent Na+ indicator sodium-binding benzofuran isophthalate. The intracellular Na+ concentration ([Na+]i) of the ATL cells was 17.1 +/- 1.7 mM (n = 22) when the ATL was microperfused in vitro with Hepes-buffered solution containing 204 mM Na+. Elimination of metabolites such as glucose and alanine from the basolateral solution increased [Na+]i. Applying either 5 mM cyanide or 5 mM iodoacetic acid to the bath also increased [Na+]i. The elimination of K+ and the addition of 10(-4) M ouabain in the bath increased [Na+]i by 25.0 +/- 5.0 mM (n = 5) in 3 min and by 10.7 +/- 2.4 mM (n = 4), respectively. The elimination of luminal and basolateral Na+ resulted in a decrease in [Na+]i, indicating Na+ permeability of both the luminal and basolateral cell membranes. The luminal Na+ permeability was not affected by furosemide. The presence of luminal Na+ permeability and the basolateral Na+/K+ ATPase suggests the presence of net active reabsorption of Na+, which is not a physiologically important amount, in our estimation.
Alanine↗
[Molecular lesion and pathophysiology of hyperglycinemia (glycine encephalopathy)].
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Amino Acid Oxidoreductases↗
New double-barreled, ion-sensitive microelectrodes for measuring intracellular Cl- activities in rabbit renal collecting ducts.
The use of the conventional ion-sensitive double-barreled microelectrodes has been unsuccessful for studying small epithelial cells such as those of the collecting duct because of the difficulty in obtaining the ideal electrodes for impaling cells. We developed a new type of ion-sensitive, double-barreled microelectrode of a size and tip configuration ideal for use in impaling small cells such as the principal cells (PCs) of the cortical collecting ducts, and remaining therein, for more than 30 min. The electrodes were pulled in two steps. The first includes the reciprocal twisting of two parallel glass capillaries, without pulling, to form a round, nontortuous fused glass capillary in the puller. In the second step, the round, fused straight capillaries are pulled so as to form the tip. This resulting procedure enabled us to impale the PCs without altering their cell membrane potentials. The basolateral membrane voltage (Vb) in PCs of the cortical collecting ducts was -69.1 +/- 1.6 mV (n = 8) and intracellular Cl- activity ([Cl]i) in PCs of the cortical collecting duct was 11.8 +/- 0.9 mmol/liter (n = 5). Changing the concentration of Cl- in the ambient solution showed that the basolateral cell membrane of the PCs was highly permeable to Cl-. This new electrode will help to obtain new information on intracellular ion handling, with the electrodes applied to the collecting duct cells.
Animals↗
Alcoholic hypertriglyceridemia with decreased activity of lipoprotein lipase and hepatic triglyceride lipase.
A 35-year-old male with alcoholic hypertriglyceridemia due to decreased lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities is reported. The patient had been drinking about 180 ml of whiskey (equivalent to 80 g of 100% ethanol) every day for the last 17 years, and the highest levels of serum triglyceride (TG) and cholesterol were 5,120 mg/dl and 506 mg/dl, respectively. Serum TG level returned to normal levels after complete alcohol abstinence. Further intake of ethanol resulted in an increase in serum TG to 326 mg/dl with a concomitant decrease in the serum levels of LPL and HTGL activities.
Adult↗
[Transurethral endoureteropyelotomy].
Transurethral endoureteropyelotomy was performed in a total of 37 patients with primary ureteropelvic junction obstruction or various ureteral strictures. Thirty-one (84%) of the 37 evaluable patients showed a radiographical improvement of hydronephrosis with a mean follow-up period of 15.8 +/- 10.5 months (range: 3-40). The clinical success rates were as follows: primary ureteropelvic junction obstruction, 11/12 92%); upper ureteral stricture, 6/7 (86%); lower ureteral stricture, 14/18 (78%). This endourological procedure required a mean operation time of 38.0 +/- 27.7 minutes and hospital stay of 7.3 +/- 4.9 days. No major complication has been identified. This retrograde procedure has a straight access to the strictured segment of ureteropelvic junction. It is safe and less invasive to the renal parenchym as it does not require percutaneous nephrostomy. Therefore, it might be clinically useful for the treatment of primary ureteropelvic junction obstruction and other ureteral strictures.
Adolescent↗
Perinatal development of amine, alcohol and phenol sulfoconjugations in the rat.
Development of the sulfoconjugating activities for amine, alcoholic and phenolic compounds was studied in hepatic 105,000 g supernatants of fetal and newborn rats. All activities in the fetus at the late stage of pregnancy were negligible or very low when compared with those of the adult female level. Amine and alcohol sulfoconjugating activities were low 2 days after birth, increased with age, and attained the adult female level 17 days after birth. In contrast, phenol sulfoconjugating activity was nearly half the level of adult female rats in the neonates 2 days after birth and was relatively constant before maturation. There were no sex-related differences in any of the activities in the immature rats, but in adult animals the activities for amine and alcohol were higher in the females than in the males; the opposite was observed for phenol sulfoconjugation.
Age Factors↗
[A new approach to intra-arterial infusion chemotherapy for breast cancer].
To perform intra-arterial infusion chemotherapy for breast cancer, we cannulated the internal thoracic and lateral thoracic arteries, respectively. In the past, we could catheterize the former vessel only 43% of the time using gross observation, but now we can do so 100% of the time with an operating microscope apparatus. It was selectively done in the latter vessel through the brachial artery after the Seldinger method. An 82-day-long intra-arterial chemotherapy could be continued without any restriction in the patient's daily life, and the tumor decreased in size considerably. Nevertheless, intra-arterial preservation of the catheter and administration of anticancer drugs decrease local blood flow and produce thromboangitis, resulting in an extremely hypovascular state of tumor lesion. These changes, observed both angiographically and fluorographically, pose problems which must be resolved for long-term intra-arterial infusion chemotherapy.
Adult↗
[Molecular lesion and pathophysiology of hyperglycinemia: glycine cleavage system, physiology and pathology].
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Amino Acid Metabolism, Inborn Errors↗
[Cerebral protection during aortic arch replacement: usefulness of continuous O2 saturation monitoring of internal jugular bulb to optimize cerebral perfusion].
How to optimize cerebral perfusion pressure and flow during selective extracorporeal circulation is a crucial problem for cerebral protection in surgical repair of aortic arch aneurysm. Among 47 cases of aortic arch replacement between 1980 and 1992, extracorporeal circulation (ECC) for the first 17 cases [group-1] were hypothermic ECC with selective cerebral perfusion (SCP) and 8 cases [group-2] with hypothermic ECC with hypothermic cardiac arrest. For the latest 16 cases [group-3] we introduced continuous O2 saturation monitoring by oximetry catheter placed in internal jugular bulb (SIJVO2) and maintained SIJVO2 value above 90% to effectively adjust pump flow to optimize cerebral perfusion pressure and flow for cerebral protection. We have retrospectively compared the effectiveness of SIJVO2 monitoring among these three groups. The mortality was 35% (6 cases: group-1), 37% (3 cases: group-2) and 6% (1 case: group-3) respectively. Cerebral dysfunction which were diagnosed in immediate postoperative period were 23% (4 cases: group-1), 0% (0 case: group-2) and 6% (1 case: group-3) respectively. We conclude continuous monitoring of SIJVO2 during selective ECC in aortic arch replacement is useful to optimize cerebral perfusion pressure and flow thereby reducing postoperative cerebral damage by selective ECC.
Adult↗
Effects of long-term anticonvulsant therapy on copper, zinc, and magnesium in hair and serum of epileptics.
The effects of long-term anticonvulsant therapy on copper (Cu), zinc (Zn), and magnesium (Mg) in the serum and hair were investigated in epileptics. Hair concentrations of Cu in both male and female epileptics, Zn in male epileptics, and Mg in female epileptics were significantly decreased when compared with those of age-matched and gender-matched controls. Hair Cu concentrations were significantly decreased in male epileptics; a significant decrease in hair Mg concentration was observed in female epileptics when compared with schizophrenics. An increased serum Cu concentration was found in female epileptics and a decreased Zn concentration was found in male epileptics. These findings suggest that long-term anticonvulsant therapy could induce alterations in both the metabolism and distribution of Cu, Zn, and Mg.
Adult↗
Defects of mitochondrial respiratory enzymes in cloned cells from MELAS fibroblasts.
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Base Sequence↗
Medium-chain acyl-CoA dehydrogenase deficiency: molecular aspects.
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is an autosomal recessive disorder which is known to cause Reye-like syndrome in children and sudden infant death. A point mutation of lysine329-to-glutamic acid329 substitution in the MCAD gene was recently identified as the most common mutation in patients with MCAD deficiency. This mutation is responsible for about 90% of mutant MCAD alleles in Caucasians. Patients with this type of mutation have a variety of symptoms, indicating that the clinical heterogeneity of MCAD deficiency may not be caused entirely by genetic heterogeneity. Screening for the mutation among newborns in England, Australia, and United States of America indicates the prevalence of carriers to be 1 in 40-107, suggesting the high incidence of the mutation. Since presymptomatic diagnosis and appropriate dietary management are important in MCAD deficiency to prevent life-threatening complications, the relatively high incidence of this disorder may warrant population screening. The most common MCAD mutation can now be detected by DNA diagnostic methods using Guthrie cards. This makes it possible to screen a population efficiently for this potentially fatal disorder.
Acyl-CoA Dehydrogenase↗
Enzymatic diagnosis of nonketotic hyperglycinemia with lymphoblasts.
We developed a new enzymatic assay for the glycine cleavage system that used Epstein-Barr virus-transformed lymphoblasts instead of liver biopsy specimens. Patients with nonketotic hyperglycinemia from a deficiency of P-protein could be clearly distinguished from control subjects by activities in their lymphoblasts, suggesting the clinical usefulness of this method.
Adolescent↗