Novel G16S (GGC-AGC) mutation in the SOD-1 gene in a patient with apparently sporadic young-onset amyotrophic lateral sclerosis.
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Adolescent↗
Biomedical subjects
K Ueda
Publications and source records attributed to K Ueda.
How does P-glycoprotein recognize its substrates?
We review how P-glycoprotein recognizes a wide variety of compounds and how it carries its substrates across membranes. Amino acid substitutions that affect the substrate specificity of P-glycoprotein have been found scattered throughout the molecule. In particular, some amino acid residues in the putative transmembrane domain (TM) 1 together with TM5-6 and TM11-12 may help to govern substrate specificity. The features that substrates for P-glycoprotein share are also discussed. The amphipathy of a substrate may decide whether the substrate can be intercalated into the lipid bilayer of the membrane. In addition, only certain molecular volumes and tertiary structures may make it possible for the substrate to fit into the substrate-binding site(s) of P-glycoprotein.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Combined thoracoscopic lung resection and laser ablation for lung cancer with pulmonary emphysema: report of a case.
We report herein the case of the 71-year-old man with lung cancer and pulmonary emphysema requiring supplementary oxygen at 21/min by nasal cannula for whom thoracoscopic wedge resection of an adenocarcinoma in his left lower lobe was successfully performed. During the same procedure, thoracoscopic laser ablation of pulmonary bullae was also carried out. There were no postoperative complications, and the patient is currently well 12 months following surgery without any evidence of local or regional recurrence, or distant metastasis. His severe dyspnea on exertion improved, and he no longer requires supplementary oxygen.
Adenocarcinoma↗
Chest wall implantation of lung cancer at the drainage tube site: report of a case.
We report herein the case of a 70-year-old man in whom a chest wall implantation of adenocarcinoma of the lung at the drainage tube site was found 4 months after a right lower lobectomy with mediastinal lymph node dissection had been performed for adenocarcinoma of the right lower lobe. The lesion was successfully treated by tumor extirpation. We believe that tumor seeding to the chest wall occurred at the time of thoracotomy. To prevent such tumor seeding, the pleural cavity should be washed out routinely with a massive volume of physiological saline solution prior to closure of the chest wall.
Adenocarcinoma↗
Acute lupus peritonitis successfully treated with steroid pulse therapy.
A 21-year-old man with systemic lupus erythematosus (SLE) who developed acute lupus peritonitis is described. Acute lupus peritonitis appeared during generalized lupus flare, with nausea, vomiting, frequent diarrhea, and abdominal tenderness with rebound and guarding. The patient was afebrile and had decreased bowel sounds. Abdominal ultrasonography and computed tomography revealed marked thickening of the gastric, duodenal, and jejunal walls, massive intraluminal fluid collection, and increasing ascites. Gastrointestinal endoscopy showed edematous mucosa with multiple erosions of the stomach and duodenum. The ascitic fluid was remarkable for low complement levels and elevated anti-DNA antibody. These manifestations of acute lupus peritonitis resolved after steroid pulse therapy with methylprednisolone. We should consider acute lupus peritonitis in a patient with SLE when abdominal symptoms are severe. Experience with our patient indicates that steroid pulse therapy is effective for this rare but severe manifestation of SLE.
Acute Disease↗
A missense mutation of the muscle glycogen synthase gene (M416V) is associated with insulin resistance in the Japanese population.
Muscle glycogen synthase (GYS1) is a key enzyme of non-oxidative pathway of glucose metabolism that has been reported to be related to insulin resistance in non-insulin-dependent diabetic (NIDDM) patients. We scanned the GYS1 gene for mutation by single strand conformational polymorphism in 244 non-obese Japanese NIDDM patients and 181 non-diabetic control subjects, and found two missense mutations; Met to Val at position 416 in the exon 10 (M416V) and Pro to Ala at position 442 in the exon 11 (P442A). The P442A mutation was found in only one NIDDM patient treated with sulfonylureas. On the other hand, the M416V mutation was widely found in the Japanese population. The mutant allele frequency in the NIDDM patients (13.7%) was slightly higher but not statistically significant compared with that in non-diabetic subjects (9.7%). However, the insulin sensitivity index [SI: x 10(-4) x min(-1) x (microU/ml)(-1)] estimated by Minimal Model analysis in the NIDDM patients carrying the M416V mutation was significantly lower than that in those without the mutation (1.18 +/- 0.27, n = 21 vs 2.20 +/- 0.20, n = 60, mean +/- SEM, p < 0.01). Glucose effectiveness, age, body mass index, and levels of glycated haemoglobin and serum lipids were not significantly different between the two groups. The same trend could be seen in non-diabetic subjects (SI: 3.70 +/- 0.46, 9 subjects with the mutation vs 5.94 +/- 0.66, 19 subjects without the mutation, p < 0.05). These findings indicate that the M416V mutation of the GYS1 gene is one of the factors contributing to the insulin resistance in the Japanese population and may play some role in the pathogenesis of NIDDM.
Adult↗
Adrenocortical function in asthmatic children: low levels of adrenocortical hormones in children with persistent attacks.
UNLABELLED: The existence of adrenal dysfunction in asthmatic patients remains controversial. Assessing adrenal function in these patients is difficult because of varying severity and duration of attacks and large fluctuations in the secretion of adrenocortical hormones. Total and free (unbound) levels of serum cortisol and cortisone were measured in asthmatic children and healthy controls using reversed-phase high performance liquid chromatography. The results were correlated with the severity and duration of asthma attacks. In asthmatic patients in remission, total and free concentrations of cortisol and cortisone did not differ significantly from those in healthy controls. During attacks, levels increased in proportion to the severity of the attack. These values decreased to control levels after 24 h. However, in children with attacks lasting for more than 5 days, values remained significantly decreased with no relation to the severity of the attack. CONCLUSION: During an asthma attack, adrenocortical hormone concentrations increase in proportion to the severity of the attack but subsequently decrease with time. It is speculated that the inability to sustain an elevated cortisol level may lead to the persistent asthma attacks.
Adolescent↗
Effectiveness of tranilast on restenosis after directional coronary atherectomy.
Tranilast is an antiallergic drug used widely in Japan that also inhibits the migration and proliferation of vascular smooth muscle cells. This pilot study was undertaken to determine the effectiveness of tranilast on restenosis after successful directional coronary atherectomy. After the procedure, 40 patients (56 lesions, tranilast group) were treated with oral tranilast for 3 months, and 152 patients (188 lesions, control group) did not receive tranilast. Angiographic and clinical variables were compared between the two groups. The minimal lumen diameter was significantly larger in the tranilast group than in the control group at both 3-month (2.08 vs 1.75 mm, p = 0.004) and 6-month follow-up (2.04 vs 1.70 mm, p = 0.003). The diameter stenosis in the tranilast group was smaller than that in the control group both 3 months (28% vs 40%, p = 0.0007) and 6 months (30% vs 43%, p = 0.0001) after the procedure, with a lower restenosis rate (percent diameter stenosis > or =50) in the tranilast group at 3 months (11 % vs 26%, p = 0.03). The number of clinical events over the 12-month period after the procedure was significantly reduced by tranilast administration (p = 0.013). These findings suggest that the oral administration of tranilast strongly prevents restenosis after directional coronary atherectomy.
Aged↗
Directional coronary atherectomy for the treatment of acute myocardial infarction.
Directional coronary atherectomy (DCA) was performed after intracoronary thrombolysis in 32 patients with a first acute myocardial infarction. DCA was successful in 31 (97%) of 32 patients. Abrupt closure of the treated segment occurred in one patient but was managed successfully by conventional balloon angioplasty. Repeat angiography was performed in 32 patients before discharge (2.7 +/- 0.7 weeks later) and in 29 patients during the follow-up (4.5 +/- 1.5 months later). No restenosis (stenosis > 50%) occurred before discharge; however restenosis occurred in 12 (41%) of 29 patients during follow-up. The restenosis rate in patients with subintimal resection was significantly higher than in those with intimal resection (78% vs 25%, p < 0.01). These data suggest that DCA in patients with acute myocardial infarction is feasible for persistent early patency of the infarct-related coronary artery, but late restenosis continues to limit success and subintimal resection may increase the restenosis rate during the follow-up.
Aged↗
Clinical implications of cigarette smoking in acute myocardial infarction: acute angiographic findings and long-term prognosis.
This study was undertaken to assess whether reperfusion in smokers could be achieved spontaneously or therapeutically and to assess whether favorable outcome in smokers could be sustained for years after infarction. We studied 260 patients with anterior myocardial infarction who underwent coronary angiography and thrombolysis within 24 hours after the onset of chest pain. There were 158 smokers and 102 nonsmokers. Smoking was associated more with men, younger age, and less multivessel disease. On initial angiography, the distribution of Thrombolysis in Myocardial Infarction grade was similar between smokers and nonsmokers. After thrombolysis, Thrombolysis in Myocardial Infarction grade 3 was more frequent in smokers (32% vs 18%; p = 0.004). In-hospital mortality rates were lower (8% vs 18%; p = 0.022) and long-term cardiac survival was better in smokers (5-year survival: 82% vs 70%; p = 0.022). Our data demonstrated that the infarct artery of smokers responded more efficiently to thrombolysis and favorable outcome in smokers was sustained throughout 5 years.
Aged↗
Effects of clomiphene citrate on the endometrial thickness and echogenic pattern of the endometrium.
OBJECTIVE: To study the effects of clomiphene citrate (CC) on the endometrium by ultrasound and to reveal the echogenic difference between the control cycle and the CC cycle. DESIGN: Retrospective study of patients before and during a CC treatment. SETTING: Department of Obstetrics and Gynecology, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan. PATIENT(S): Seventy-nine infertile women who had a spontaneous ovulation and a normal luteal function. INTERVENTION(S): Patients received 50 mg/d CC between days 5 and 9 of the menstrual cycle. MAIN OUTCOME MEASURE(S): Endometrial thickness, echogenic pattern of the endometrium, serum E2 content, and E2 and P receptor contents in the endometrium. RESULT(S): Endometrial thickness was significantly thinner during the CC cycle (7.6 +/- 1.4 mm, mean +/- SD, n = 79) than during the control cycle (8.5 +/- 1.7 mm, n = 79) on late proliferative days, but there was no significant difference on midsecretory days (10.8 +/- 2.2 mm during the CC cycle, n = 79; 11.2 +/- 2.2 mm during the control cycle, n = 79). The echogenic patterns, however, were different between the two cycles on midsecretory days. Moreover, the incidence in which patients showed a grade 3 endometrium on midsecretory days was significantly higher during the conceived CC cycle compared with the not-conceived CC cycle. Serum E2 levels were significantly higher, but E2 receptor contents in the endometrium were significantly lower during the CC cycle (67 +/- 46 fmol/mg, n = 13) compared with the control cycle (123 +/- 89 fmol/mg, n = 15) on late proliferative days. CONCLUSION(S): Clomiphene citrate affected the echogenic pattern of the endometrium, and most of the endometrium showed a grade 3 pattern on midsecretory days during the conceived CC cycle. Under the CC treatment, the comfortable endometrium for embryos might be different from the control cycle.
Adult↗
Arterial ketone body ratio as a prognostic indicator in acute heart failure.
The arterial ketone body ratio (AKBR), an established clinical tool that reflects hepatic mitochondrial oxidation-reduction potential, predicts the outcome of patients with shock and multiple organ failure and the postoperative outcome in patients who have undergone major liver or heart surgery. The purpose of this study was to determine the prognostic significance of AKBR in patients with acute heart failure. The subjects of this study were 52 patients with acute heart failure. The following parameters were analyzed after Cox univariate hazard analysis was performed: AKBR, plasma norepinephrine, left ventricular ejection fraction, cardiac index, pulmonary arterial wedge pressure, sex, age, human atrial natriuretic peptide, endothelin-1, and cholesterol. The follow-up period was 30 weeks with cardiac death as the end point. Stepwise multivariate proportional hazard analysis revealed that AKBR was the most significant predictor of death, followed by norepinephrine and human atrial natriuretic peptide. Curve-fitting analysis revealed that the relationship between log (norepinephrine) and AKBR could best be described by two distinct lines, with their intersection at AKBR = 0.7 and norepinephrine = 418. With these results we conducted Kaplan-Meier analysis for AKBR > or = 0.7 and AKBR <0.7. The survival rate in patients with AKBR > or = 0.7 was 100%, whereas that in patients with AKBR <0.7 was 15% (p < 0.0001, log-rank analysis). These results indicate that AKBR is a novel independent predictor of death in heart failure.
Acute Disease↗
Mechanism for reduction of serum folate by antiepileptic drugs during prolonged therapy.
To determine whether the induction of liver enzymes by antiepileptic drugs play a major role in folate depletion, serum concentrations of folate were measured in age-matched control subjects without anemia and in epileptic outpatients who were being treated with a single antiepileptic drug. Two of the four drugs being administered were enzyme inducers. A protein binding radioassay was used to measure folate levels. Compared with serum folate levels in controls (5.14 +/- 1.88 ng/ml: n = 74), mean serum folate levels were reduced significantly in patients treated with phenobarbitone (3.91 +/- 1.73 ng/ml, p < 0.01: n = 33) and carbamazepine (3.85 +/- 1.02 ng/ml, p < 0.01: n = 36): both of which are enzyme-inducing agents. In contrast, patients treated with the non-enzyme-inducer valproate (5.39 +/- 1.71 ng/ml: n = 41) or zonisamide (5.59 +/- 2.60 ng/ml: n = 25) exhibited serum folate levels that did not differ significantly from values in controls. Findings showed that a reduction in serum folate is associated with the induction of enzymes by antiepileptic drugs. Thus, the induction of microsomal liver enzymes may be critical to the depletion of folate by antiepileptic drugs.
Adolescent↗
Plasma total homocysteine concentrations in epileptic patients taking anticonvulsants.
Plasma total homocysteine (tHcy) and serum folate (FA) concentrations were measured in 130 epileptic patients taking anticonvulsant drugs. A significant inverse correlation was found between FA and tHcy. This was greater in the older group (> or = 15 years) than in the younger group (1 to 14 years). There were four FA-deficient patients (FA concentration < 3 ng/mL regardless of symptoms), including three patients in the older group and one in the younger group. All FA-deficient patients had received long-term treatment (> 7 years) with multiple anticonvulsants. Their tHcy levels were higher than the 90th percentile of those in control subjects. Two patients showed extremely high levels of tHcy (57.9 and 29.1 mumol/L) and subnormal plasma methionine levels. After FA therapy, their tHcy decreased to levels the same as or less than those of control subjects and FA increased to above the normal range. Based on these findings, we conclude that measuring FA and tHcy concentrations may be useful for preventing thrombosis due to hyperhomocysteinemia in epileptic patients taking anticonvulsants, particularly those who receive long-term treatment with multiple agents.
Adolescent↗
Serum concentrations of cortisone and cortisol in premature infants.
To determine the relationship between biological active cortisol and its inert metabolite cortisone accurately in premature infants, serum cortisone and cortisol concentrations were measured by reversed-phase high-performance liquid chromatography (HPLC) in a group of 232 premature infants and in a control group of 127 children and 88 adults. In the control group, serum cortisone concentrations were greater than serum cortisol levels during the first 2 months after birth; cortisol levels were higher than cortisone levels after 2 months of age. However, in premature infants, serum cortisone concentrations were greater than serum cortisol levels even after the first 2 months, and total concentrations of cortisone and cortisol were equal to those in controls. Results were then analyzed according to the equivalent gestational age of premature infants. Cortisone was predominant in premature infants older than 32 weeks of equivalent gestational age, but cortisol was higher than cortisone from equivalent gestational age 24 to 31 weeks. These findings suggest that the ability of premature infants to secrete glucocorticoids resembled that of normal controls. Also, the fetal zone of the cortex, which is associated with a predominance of cortisone, remained functional in premature infants for a longer time than in control infants. Our findings that in premature infants cortisone was predominant compared with cortisol and the sum of cortisone and cortisol was equal to that in the controls indicate that cortisone cannot be disregarded whenever the cortisol level is estimated, although cortisone itself is recognized to be biologically inactive. Simultaneous measurement of serum cortisone and cortisol concentrations is important when adrenocortical function is being determined, especially in premature infants.
Adolescent↗
Prevalence of the Trp64Arg missense mutation of the beta3-adrenergic receptor gene in Japanese subjects.
Prompted by the recent findings that a tryptophan to arginine (Trp64Arg) mutation in the beta3-adrenergic receptor gene was associated with an earlier onset of non-insulin-dependent diabetes mellitus (NIDDM) in Pima Indians, with abdominal obesity and insulin resistance in Finns, and with an increased capacity to gain weight in French whites, we studied the prevalence of this mutation in 231 diabetic and 95 nondiabetic Japanese subjects and assessed its contribution to the development of obesity and NIDDM. The allelic frequencies of the mutation were 0.18 in diabetic and 0.23 in nondiabetic subjects, showing no significant difference between the two groups (P = .067). In nondiabetic subjects, body mass index (BMI) did not differ between those with and without the mutation (22.2 +/- 3.5 v 21.4 +/- 3.2 kg/m2, P = .252). In NIDDM subjects, BMI at the time of study and maximal BMI before the start of treatment did not differ between those with and without the mutation (22.8 +/- 2.6 v 23.2 +/- 3.7 kg/m2, P = .678, and 24.7 +/- 2.6 v 24.9 +/- 3.1 kg/m2, P = .277). Homozygotes for the mutation did not have trends to have increased BMI in either diabetic or nondiabetic subjects. The age at diagnosis of NIDDM also did not differ between the two groups (48.8 +/- 9.9 v 47.8 +/- 12.5 years, P = .796). Fasting serum cholesterol and triglyceride levels and systolic and diastolic blood pressure before the start of treatment did not differ between NIDDM subjects with and without the mutation. In conclusion, although the Trp64Arg mutation is not uncommon in Japanese, it does not appear to be associated with obesity, NIDDM, age at diagnosis of NIDDM, or dyslipidemia. Our results suggest that the mutation has minor effects, if any, on the development of obesity and NIDDM in Japanese.
Adult↗
Intrapulmonary Mycobacterium avium infection as the first manifestation of chronic granulomatous disease.
A 10-month-old Japanese male infant, with no history of being prone to infections, contracted an intrapulmonary mycobacterial infection. After 2 months of intermittent fever, radiological examinations revealed mass lesions in the lung and mediastinum. Biopsy specimens showed granulomas with caseous necrosis, from which Mycobacterium avium was isolated. There was no history of mycobacteriosis or immunodeficiency diseases among his relatives. Analyses of the O2- release and expression of NADPH oxidase components verified that he suffered from gp91-phox- chronic granulomatous disease (CGD), and that his mother was a carrier of the disease. This is a rare clinical presentation for the onset of CGD, suggesting that the invasive mycobacteriosis might result from defective intracellular killing of CGD-phagocytes.
Granulomatous Disease, Chronic↗
Cleavage of viral RNA and inhibition of viral translation by hepatitis C virus RNA-specific hammerhead ribozyme in vitro.
BACKGROUND/AIMS: A hammerhead ribozyme has been used as a new way to suppress specific gene expression. We designed hammerhead ribozymes directed against hepatitis C virus RNA, and investigated their cleavage efficiency and inhibitory effect on viral translation in vitro. METHODS: Three hammerhead ribozymes bearing different cleavage sites in the core region of hepatitis C virus RNA (genotype 1b) were designed in this study. Ribozymes and the target hepatitis C virus RNA were synthesized by in vitro transcription. The cleavage efficiency was evaluated by the ribozyme cleavage assay. The inhibitory effect of the ribozyme on viral translation was further studied by the viral translation inhibition assay. RESULTS: All ribozymes specifically cleaved the target RNA of 1217 bases at a physiological temperature in a dose-dependent manner, with the specific cleavage increasing with a longer incubation period. The target RNA was cleaved most efficiently by the ribozyme with the cleavage site located nearest to the initiation codon. In the viral translation inhibition assay, all ribozymes showed a significant inhibitory effect on viral translation. The ribozyme with the cleavage site located farthest from the initiation codon blocked viral translation most efficiently, and demonstrated almost 70 to 80% inhibition. For ribozymes with the T7 transcription terminator sequence, both the target RNA cleavage and the inhibition of viral translation tended to be achieved less efficiently by ribozymes with T7 terminator than by those without it. CONCLUSIONS: These findings suggest that ribozyme-mediated hepatitis C virus RNA cleavage may serve as a new strategy in the treatment of hepatitis C virus infection.
Hepacivirus↗