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Biomedical subjects

S Ikawa

Publications and source records attributed to S Ikawa.

At least 19 recordsLinked to original sources

An interaction between p21ras and heat shock protein hsp60, a chaperonin.

Ras proteins play a crucial role in the development of neoplasia and in signal transduction in normal cells. In a search for proteins interacting with p21ras, we previously identified a protein of 60 kDa (p60) through use of a chemical cross-linker. Using information from partial amino acid sequencing of the purified protein, we isolated full-length cDNA clones encoding this 60-kDa protein. Nucleotide sequence analysis revealed that p60 is the murine heat shock protein hsp60, a chaperonin. Association of hsp60 with p21ras appears physiological, as the amount of hsp60 complexed to p21ras was similar even in cells over-expressing p21ras, and reversing the order of cross-linking and lysis of the cells, which releases large amounts of hsp60 from mitochondria, did not alter the amount of hsp60 cross-linked to p21ras.

Amino Acid Sequence

Synthesis of sulfonate analogs of bile acids.

Sulfonate analogs of C23 and C24 bile acids were synthesized from norcholic, norchenodeoxycholic, norursodeoxycholic, nordeoxycholic, norhyodeoxycholic, cholic, deoxycholic, hyodeoxycholic, and lithocholic acids. The principal reactions used were (1) reduction of the bile acids with NaBH4 to the corresponding bile alcohols, (2) selective tosylation of the terminal hydroxyl group, (3) iodination of the tosyl esters with NaI, and (4) treatment of the iodides with Na2SO3 to form the sulfonate analogs of the bile acids. The sulfonate analogs showed polarity similar to that of taurine-conjugated bile acids on thin-layer chromatography. The carbon 13 nuclear magnetic resonance spectral data for the sulfonate analogs were tabulated.

Bile Acids and Salts

Decreased superoxide dismutase activity in erythrocyte in Parkinson's disease.

Superoxide dismutase (SOD) activities in Parkinson's disease (PD) were significantly lower than those in controls, especially in a treated PD group. However, SOD activities in an untreated PD group did not decrease. There was a significant correlation between SOD activities and the duration of illness in the treated PD group (p < 0.05). There was a significant correlation between SOD activities and the present doses of L-DOPA/carbidopa in the treated PD group.

Aged

[A case report of tetralogy of Fallot associated with total occlusion of the right coronary artery and complicated with infective endocarditis].

A 31-year-old male with tetralogy of Fallot (TF) and total occlusion of the right coronary orifice complicated with infective endocarditis successfully underwent total repair of TF and coronary artery bypass graft (CABG). The patient had severely suffered from symptoms including breathlessness, palpitation (SVT) and chest pain. The coronary arteriography revealed occlusion of the right coronary orifice. The preoperative course was further complicated by endocarditis with vegetation of the aortic valve that did not respond to antibiotics. Concomitant surgical procedures consisting of TF repair, CABG to the right coronary artery with saphenous vein graft and vegetectomy of the aortic valve were carried out. The postoperative course was uneventful though he underwent cholecystectomy for symptomatic gall stones after TF repair. The patient is now in NYHA class II.

Adult

Pulmonary artery morphology and hemodynamics in pulmonic valve atresia with ventricular septal defect before and after repair.

Cardiac catheterization and angiography were performed in 22 patients with pulmonic valve atresia and ventricular septal defect to evaluate pulmonary morphology and hemodynamics before and after repair. In 12 of the 22, pulmonic valve atresia and ventricular septal defect were associated with major aortopulmonary collateral arteries, which were ligated in most. Mean postoperative pulmonary artery pressure (PAP) ranged from 9 to 92 mm Hg (mean 28 +/- 19) and pulmonary vascular resistance ranged from 1.1 to 35.2 U.m2 (mean 6.4 +/- 8.0). These data correlated (r = 0.89, p less than 0.001). The number of pulmonary artery subsegments connected to the central pulmonary arteries was 22 to 42 (mean 38 +/- 6). Univariate analysis revealed that the mean postoperative PAP correlated with the number of pulmonary artery subsegments connected to the central pulmonary arteries (r = -0.81, p less than 0.001), with mean postoperative PAP (r = 0.79, p less than 0.001), with the postoperative pulmonary artery area index of the right and left pulmonary arteries at prebranching (r = -0.76, p less than 0.001), and with the sum of the pulmonary artery areas after branching (r = -0.69, p less than 0.005). Pulmonary vascular resistance correlated with the number of pulmonary artery subsegments connected to the central pulmonary arteries (r = -0.85, p less than 0.001), with the mean preoperative PAP (r = 0.79, p less than 0.001), with the sum of the pulmonary artery areas after branching (r = -0.73, p less than 0.001), and with the postoperative pulmonary artery area index (r = -0.70, p less than 0.001). The incidence of pulmonary vascular resistance being less than 3 U.m2 was significantly higher in patients with greater than 36 pulmonary artery subsegments connected to the central pulmonary arteries and with a preoperative pulmonary artery area index greater than 0.5 (88%) (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

False aneurysm formation of the great arteries after arterial switch operation.

An infant with simple transposition of the great arteries underwent a two-staged arterial switch operation, after which mediastinal infection occurred. Continuous irrigation with povidone-iodine solution was performed for 10 days. After that, the patient experienced life-threatening hemorrhage three times. At the time of the second hemorrhage, greater omental transfer was performed. On postoperative day 109, false aneurysm was recognized, having developed from both great arteries. Successful repair was performed on postoperative day 110.

Aneurysm

Metabolism of sodium 3 alpha,7 alpha-dihydroxy-5 beta-cholane-24-sulfonate in hamsters.

Metabolism of sodium 3 alpha,7 alpha-dihydroxy-5 beta-cholane-24-sulfonate, the sulfonate derivative of chenodeoxycholic acid, was studied in hamsters. In bile fistula hamsters, the sulfonate analogue was efficiently absorbed from the ileum and secreted rapidly into the bile without any modification such as conjugation. However, absorption from the jejunum was smaller than that observed for the ileum. After oral administration, the sulfonate analogue of chenodeoxycholic acid was recovered quantitatively in the feces as the unchanged form in contrast to simultaneously administered chenodeoxycholic acid, which was entirely converted to lithocholic acid during its passage through the intestinal tract. These results demonstrate that the sulfonate analogue is absorbed mainly from the ileum by active transport, enters the enterohepatic circulation like the endogenous conjugated bile acids, and completely resists bacterial degradation.

Animals

[The mechanisms of exercise-induced proteinuria--relationship between urinary excretion of proteins and lactate after exhaustive exercise].

Exercise-induced proteinuria is of the mixed glomerular-tubular type and has been thought to be due to increased glomerular permeability to macromolecular proteins in response to activation of the renin-angiotensin system and catecholamines and a reduction in renal hemodynamics. The excretion of the tubular type of proteins, however, can't be explained by the above mechanism. Two groups, consisting of subjects with the highest (H-alb, n = 20) and the lowest (L-alb, n = 20) excretion of albumin 30 min after exhaustive exercise were selected from a total of 69 normal male participants. No differences in VO2max, maxHR, changes in plasma angiotensin II, catecholamines, urine volume, or Ccr following exercise were observed between the two groups. The increase in blood lactate concentration immediately after exercise, increases in urinary excretion of lactate, pyruvate, alpha 1 M, beta 2 M, albumin and decrease in Cl- excretion 30 min after exercise in the H-alb group were significantly greater than in the L-alb group. The greater the urinary excretion of lactate and pyruvate, the greater the excretion of albumin, alpha 1M and beta 2M, and the less the urinary excretion of Cl-. The coefficient of correlation between the urinary excretion of lactate and beta 2M was 0.757, and between urinary excretion of albumin and beta 2M, 0.756 (p less than 0.001). These results suggest that exercise-induced organic acids and/or decrease in renal circulatory pH caused by organic acids may alter renal glomerular permeability and inhibit renal tubular reabsorption of low molecular weight proteins (alpha 1M, beta 2M). The permeability of the glomerular basement membrane (GBM) to macromolecular proteins may be altered by a reduction in the charge barrier of the GBM, which may be caused by the over-production of organic acids and a lower pH.

Adult

[Late postoperative pulmonary vascular resistance in patients with tetralogy of Fallot and pulmonary atresia].

Twenty-two patients with tetralogy of Fallot and pulmonary atresia underwent cardiac catheterization and angiocardiography late after repair. In ten patients, the disease was not associated with the major aortopulmonary collateral artery (MAPCA), but in 12 patients, the disease was associated with it. Three patients died after restudy, two because of pulmonary hypertension and one because of pneumonia. Pulmonary artery mean pressure was 15-92 (28 +/- 21) mmHg, being higher in 75% of the patients with MAPCA than the normal range. The number of pulmonary artery subsegments connected to the central pulmonary arteries was determined from pulmonary arteriography, being 22-42 (38 +/- 6). Pulmonary artery mean pressure and pulmonary vasculature resistance (PVR), 0.8-35.2 (10 +/- 9), inversely correlated with the number of the centrally connected pulmonary artery subsegments (r = -0.81, p less than 0.001 vs PAP, r = -0.85, p less than 0.001 vs PVR). PVR per subsegment also inversely correlated with them (r = -0.81, p less than 0.001). These findings suggest that pulmonary vasculature resistance is abnormally high in this disease, and increase as the number of the centrally connected pulmonary artery subsegments decrease.

Adolescent

Hemodynamic effects of bidirectional cavopulmonary shunt with pulsatile pulmonary flow.

The effects of "pulsatile" bidirectional cavopulmonary shunt (BCPS) produced by the flow from the ventricle or Blalock-Taussig (B-T) shunt on ventricular function and pulmonary circulation were evaluated in 10 patients with univentricular heart from 3 to 37 months (mean, 16.6 +/- 9.5 months) after surgery. Age at operation ranged from 7 months to 15 years (mean, 5.5 +/- 4.5 years). In addition to the BCPS, pulmonary flow was supplied from a B-T shunt on the contralateral side of the BCPS in five patients, from the ventricle through the stenotic pulmonary valve in four patients, and from both the ventricle and a B-T shunt in one patient. There were no operative deaths; however, there were two late deaths from acute respiratory infection 10 and 13 months after operation. Mean pulmonary arterial pressure measured the first day after operation ranged from 10 to 19 mm Hg (mean, 14 +/- 3 mm Hg). Mean pulmonary arterial pressure at postoperative cardiac catheterization was less than 15 mm Hg (mean, 12 +/- 4 mm Hg). Pulse pressure ranged from 3 to 12 mm Hg (mean, 7 +/- 4 mm Hg). Arterial oxygen saturation increased significantly from 77 +/- 5% before BCPS to 86 +/- 4% immediately after discharge from the intensive care unit (p less than 0.005) and 85 +/- 3% (p less than 0.025) at late cardiac catheterization. Pulmonary arteriovenous fistula was not detected in contrast echocardiography and pulmonary arteriography. Systemic ventricular end-diastolic volume index decreased significantly (p less than 0.01) from 141 +/- 54 ml/m2 before BCPS to 98 +/- 35 ml/m2 1 month after BCPS by echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical

A missense mutation found in human lactate dehydrogenase-B (H) variant gene.

A human lactate dehydrogenase-B mutant gene was isolated from a genomic DNA library constructed from a patient with unstable LDH-B (heart) subunit. The nucleotide sequences of seven protein-coding exons were determined and a single nucleotide substitution of G by A at Arg codon CGC in exon 4 was found. This mutation results in an amino-acid replacement of a conserved arginine by histidine at the residue "173," which is involved in an anion-binding site at the P-axis of LDH subunits.

Adult

[Circadian variations of urinary excretions of microproteins and N-acetyl-beta-D-glucosaminidase (NAG) during the ordinary activity day].

The present investigation was performed to confirm the relationship between the circadian variation of microproteinuria and physical activity. Urine samples from 10 normal male volunteers, collected during six consecutive 4-h periods, were examined for albumin, alpha 1-, beta 2-microglobulin, NAG, electrolytes and hormones. The fluctuations in heart rate (HR) and blood pressure (BP) over 24-h were measured at 30-min and 1-h intervals, respectively. Energy expenditure (EE) was calculated using the equation of regression between HR and oxygen uptake measured on another day. The variations of HR (delta HR) and EE (delta EE) based on a 24-h average (bpm and kcal/kg/h) were used as indices of change in physical activity during an ordinary day. The correlation coefficients between delta HR and the variations of albumin (delta Alb) and beta 2-microglobulin (delta beta 2M) from the 24-h average (micrograms/h.cr 1 mg) were 0.619 and 0.670 (p less than 0.001), respectively. Increased excretions of both glomerular and tubular proteins were correlated with the increase in HR and/or EE during daytime activity. During rest time at night, the variations in alpha 1M, beta 2M and NAG excretion were different from the variations in albumin. A temporary inhibition of tubular protein excretion was observed only in the early morning (04:00-08:00), although albumin excretion was inhibited throughout the nighttime. These findings suggested that physical activity may influence the diurnal variations in protein excretions, that albuminuria may be more sensitive to daytime activity, and that fluctuation of tubular protein excretion may be preferably controlled by an endogenous mechanism. Timed overnight or first-morning urine may be recommendable as a sample for determination of microalbuminuria for screening of clinical diabetic nephropathy.

Acetylglucosaminidase

Sex differences in blood constituents of rats following tail suspension.

Tail suspension was utilized to study sex differences in the effects of hypokinesia on blood constituents of rats. Twelve male and twelve female rats were used. After four weeks of exposure to tail suspension or non-treatment, the rats were laparotomized under ether anesthesia and blood samples were obtained. Biochemical tests on the blood samples were then performed immediately. Hematocrit and serum iron were also estimated. The results were as follows: 1) The same tendencies were noted in blood constituents between male and female rats in the control group and the tail suspension group. 2) The average levels of blood albumin, creatinine, uric acid, glucose, triglyceride, serum iron and hemoglobin in the tail suspension group were lower than those in the control group, especially in male rats.

Animals

Synthesis of new bile salt analogues, sodium 3 alpha, 7 alpha-dihydroxy-5 beta-cholane-24-sulfonate and sodium 3 alpha, 7 beta-dihydroxy-5 beta-cholane-24-sulfonate.

This report describes the chemical synthesis of two new bile salt analogues, namely sodium 3 alpha,7 alpha-dihydroxy-5 beta-cholane-24-sulfonate and sodium 3 alpha,7 beta-dihydroxy-5 beta-cholane-24-sulfonate from chenodeoxycholic acid and ursodeoxycholic acid, respectively. Each common bile acid was converted into the corresponding 5 beta-cholane-3,7,24-triol by treatment with ethyl chloroformate in the presence of triethylamine followed by sodium borohydride reduction. Reaction of the cholanetriol with p-toluenesulfonyl chloride at 4 degrees C afforded the partially tosylated product, 24-p-toluenesulfoxy-5 beta-cholane-3,7-diol, which was then treated with sodium iodide to produce 24-iodo-5 beta-cholane-3,7-diol. The 24-iodide was refluxed with sodium sulfite in aqueous ethanol to give the desired sulfonate analogue of the naturally occurring bile acid, chenodeoxycholic acid or ursodeoxycholic acid.

Bile Acids and Salts

Defective homologous pairing and proficient processive unwinding by the recA430 mutant protein and intermediates of homologous pairing by recA protein.

The recA protein promotes the formation and processing of joint molecules of homologous double- and single-stranded DNAs in vitro. Under a set of specified conditions, we found that the substitution of a single amino acid in the recA protein (recA430 mutation) depresses its activity for the homologous pairing to about 1/100 of that by the wild type protein when compared by the rate for the first 2-3 min of the reaction, but that the mutation only slightly, if at all, affects its ability to bind progressively to double-stranded DNA to unwind the double helix ("processive unwinding"). This is in striking contrast to an anti-recA protein monoclonal IgG, ARM193, which severely inhibits the processive unwinding but not the homologous pairing, providing further support for our conclusion that the homologous pairing and processive unwinding are functionally independent of each other. Antibody ARM193 caused the breakdown of spontaneously formed filaments of the recA protein, but the recA430 mutation did not affect the self-polymerization of the protein. The recA430 protein was apparently proficient in the functional binding to a single-stranded DNA and in the hydrolysis of ATP. However, we found that under the above conditions the mutant protein was defective as to homology-independent conjunction of DNA molecules to form a "ternary complex" (of macromolecules). These results suggest that (i) only one DNA-binding site is sufficient for the recA protein to promote the processive unwinding (the ability of the protein to form spontaneous filaments is closely related to this process) and that (ii) two DNA-binding sites on each of the recA polypeptides or those composed of a dimer (or oligomer) of the polypeptide are required for the recA protein to promote both the conjunction of parental DNA molecules and the homologous pairing (the ability to form the spontaneous filaments is not essential to this process). (iii) The simultaneous inactivation of the activity to promote the homologous pairing and that to form the ternary complex by the single substitution of the amino acid provides a physical support for the conclusion that the ternary complex is an indispensable intermediate in the homologous pairing.

Adenosine Triphosphatases

Apolipoprotein abnormalities in dementia.

The serum levels of apolipoprotein B, C-II and the ratio of apolipoprotein B/A-I were found to be significantly higher in multiinfarct dementia than in dementia of the Alzheimer type. The high serum levels of apolipoprotein B, C-II and the high ratio of apolipoprotein B/A-I may cause multiinfarct dementia. The large difference between the groups suggests that the serum levels of apolipoprotein B, C-II and the ratio of apolipoprotein B/A-I may be useful in differential diagnosis of these two kinds of dementia.

Aged

Effect of bile duct ligation on bile acid and cholesterol metabolism in rats.

The effects of bile duct ligation on bile acid and cholesterol metabolism were examined in male Wistar strain rats. Quantitative and qualitative changes of bile acids and cholesterol in serum and urine occurred; beta-muricholic acid predominantly increased in serum and urine and the ratio of urinary cholic acid and beta-muricholic acid changed from about 5:3 on day 1 to about 1:8 on day 5 under biliary obstruction. The form of the increased urinary bile acids was mainly taurine-conjugated and partly sulfated. Under conditions of bile duct ligation on day 5, 14C-labeled 3 beta-hydroxy-5-cholenoic, lithocholic, and chenodeoxycholic acids were intragastrically administered to the rats after pretreatment with antibiotics and the metabolites of these three acids were investigated. 3 beta-Hydroxy-5-cholenoic acid was most efficiently converted to beta-muricholic acid. The present study strongly suggested the presence of an alternative metabolic pathway induced by bile duct ligation, which caused the change in composition of urinary bile acids, and especially the marked increase in beta-muricholic acid formation. A possible alternative pathway for bile acid biosynthesis under biliary obstruction in rats is postulated.

Animals