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Biomedical subjects

K Sakai

Publications and source records attributed to K Sakai.

At least 541 records · Page 30Linked to original sources

Characterization of poly-leucine substituted analogues of the human surfactant protein SP-C.

A series of novel amphipathic peptides constituted of an N-terminal hydrophilic portion (CPVHLKR, residues 6-12) of human pulmonary surfactant protein-C (SP-C) and a poly-leucine (poly-L) stretch of various chain lengths as the C-terminal hydrophobic tail were synthesized and evaluated relevant to their ability to improve the surface activity of a ternary lipid mixture composed of dipalmitoylphosphatidylcholine, egg-phosphatidylglycerol and palmitic acid (DPPC/E-PG/PA, 75:25:10, w/w) in a Langmuir-Wilhelmy surface balance. CPVHLKRL11, a human SP-C analogue bearing an 11-residue poly-L tail, and its related peptides with longer tails in the ternary lipid mixture, accelerated not only the surface spreading at the air-water interface but also exhibited significantly improved dynamic surface activity, compared to the ternary lipid mixture. Their surface activities were almost indiscernible from those of the synthetic human SP-C. When reconstituted into a ternary lipid mixture containing members of the homologous series of n-saturated diacylphosphatidylglycerol, the surface activities of the poly-L analogues were almost completely unaffected, whereas replica peptides carrying the hydrophobic portion of native SP-C were found to have distinct surface activities depending upon the acyl-chain lengths of phosphatidylglycerol. The poly-L stretch of a poly-L analogue could be replaced with poly-norleucine of the same chain length without a significant loss of surface activity. Substitution of the poly-L portion in the analogues with poly-valine or poly-isoleucine resulted in a considerable decrease in surface activity. The poly-L analogue in the DPPC/E-PG/PA mixture was demonstrated to act as an excellent surfactant comparable with Surfacten, a modified bovine surfactant preparation that was used for treatment for infant respiratory distress syndrome, based on evaluation of the lung pressure-volume characteristics using premature rabbit neonates.

Amino Acid Sequence↗

Identification and characterization of a protein found after X-irradiation in human T cell leukemia.

An X-ray-induced protein in human T cell leukemia MOLT-4 cells is described. It was detected 4 hrs after irradiation by two dimensional gel electrophoresis and silver staining. The location is 41 kDa in the mass and 4.0 of pI. Its spots were collected from the gels and microsequenced. The protein was identified from its partial sequences as a set gene product, whose gene translocation previously was found in a case of acute undifferentiated leukemia. Polyclonal rabbit antibodies stained two spots, the 41 kDa (p 41) and the 42 kDa (p 42) proteins. Photoimage analyses of the silver-stained gels and Western blots indicated that the induction of p 41 was time dependent, starting 4 hrs after irradiation and reaching a plateau by 10 hrs, and was dose dependent between 1 and 10 Gy. p 41 appeared somewhat ahead of cell death, as determined by the dye exclusion test, but the role in that cell process has yet to be clarified.

Amino Acid Sequence↗

Biodegradation of cellulose acetate by Neisseria sicca.

Bacteria capable of assimilating cellulose acetate, strains SB and SC, were isolated from soil on a medium containing cellulose acetate as a carbon source, and identified as Neisseria sicca. Both strains degraded cellulose acetate membrane filters (degree of substitution, DS, mixture of 2.8 and 2.0) and textiles (DS, 2.34) in a medium containing cellulose acetate (DS, 2.34) or its oligomer, but were not able to degrade these materials in a medium containing cellobiose octaacetate. Biodegradation of cellulose acetate (DS, 1.81 and 2.34) on the basis of biochemical oxygen demand reached 51 and 40% in the culture of N. sicca SB and 60 and 45% in the culture of N. sicca SC within 20 days. A decrease in the acetyl content of degraded cellulose acetate films and powder was confirmed by infrared and nuclear magnetic resonance analyses. After 10-day cultivation of N. sicca SB and SC, the number-average molecular weight of residual cellulose acetate decreased by 9 and 5%, respectively. Activities of enzymes that released acetic acid and produced reducing sugars from cellulose acetate were mainly present in the culture supernatant. Reactivity of enzymes for cellulose acetate (DS, 1.81) was higher than that for cellulose acetate (DS, 2.34).

Acetic Acid↗

Chemical modification of histidine residue of N-acyl-D-Glutamate amidohydrolase from Pseudomonas sp. 5f-1.

N-Acyl-D-glutamate amidohydrolase (D-AGase) from Pseudomonas sp. 5f-1 was inactivated by diethyl pyrocarbonate (DEP). The chemical modification by DEP showed a difference spectrum at 246 nm due to the N-carbethoxyhistidine residue. Removal of the carbethoxy group from inactivated enzyme with hydroxylamine restored enzyme activity. The inactivation by DEp proceeded with pseudo-first-order kinetics, and was protected in the presence of the substrate N-acetyl-D-glutamate (Glu), or the competitive inhibitor sodium alpha-ketoglutarate (alpha-KGA). These results suggest the presence of an essential histidine residue at or near of the active site of the enzyme.

Amidohydrolases↗

[Antigenicity studies of prulifloxacin (NM441)].

Antigenicity of prulifloxacin, a new antibacterial agent, and that of its active metabolite (NM394) were investigated using guinea pigs and mice in this study. In the study with guinea pigs, the animals were immunized with prulifloxacin by oral administration, the predetermined clinical route, and with prulifloxacin alone or emulsified with Freund's complete adjuvant (FCA) by s.c. When active systemic anaphylaxis (ASA) test and passive cutaneous anaphylaxis (PCA) test of these animals were conducted by eliciting with NM394 alone or protein conjugate (NM394-GPSA) of NM394 and guinea pig serum albumin (GPSA), no ASA and PCA reactions were observed. When guinea pigs were immunized subcutaneously with protein conjugate (NM394-BSA) of NM394 and bovine serum albumin (BSA) together with FCA, ASA and PCA reactions were positive by eliciting with NM394-GPSA or NM394-BSA, but were negative by eliciting with NM394 alone. In the study with mice, the animals were immunized orally with prulifloxacin and intraperitoneally with prulifloxacin alone or suspended with aluminum hydroxide gel (alum). When rat PCA test of sera from these mice was conducted by eliciting with NM394 or NM394-GPSA, no positive PCA reaction was observed. When mice were immunized intraperiotneally with NM394-BSA together with alum, PCA reactions were positive by eliciting with NM394-GPSA or NM394-BSA, but were negative by eliciting with NM394 alone. These results show that prulifloxacin has no immunogenicity to guinea pigs and mice, and NM394 as its active form has no eliciting potential to anti-NM394-BSA antibody.

Anaphylaxis↗

[A case of idiopathic orthostatic hypotension manifesting sick sinus syndrome due to sympathetic nervous dysfunction].

A 67-year-old woman with idiopathic orthostatic hypotension was presented. The patient started to experience faintness on standing since 1993. During a physical examination, her systolic blood pressure fell from 148 to 50 mmHg on standing. Blood pressure responses to the mental arithmetic test and hyperventilation stress were normal. However, cold pressor test failed to increase blood pressure. These observations, with the finding that phase IV response on Valsalva's maneuver was absent, indicate afferent sympathetic nervous dysfunction. Peripheral neuropathy including diabetes mellitus and involvement of central nervous system such as multiple system atrophy were excluded. Holter ECG examination revealed a 3.9 second sinus arrest and bradycardia (total beats 88901/day). the blunted responses of the heart rate to atropine as well as isoproterenol further suggested the presence of sick sinus syndrome. Amezinium administration significantly improved her orthostatic hypotension and eliminated sinus arrest. These findings indicate that sympathetic nervous dysfunction could account for at least a part of the sick sinus syndrome in this patient.

Aged↗

Reconstruction of irreparable brachial plexus injuries with reinnervated free-muscle transfer. Case report.

The complete avulsion of the brachial plexus is a severe injury usually caused by high-energy trauma. Even with the advent of modern microsurgical techniques, many patients have been rendered severely handicapped following this injury. The authors present a new reconstructive procedure that uses a microsurgical reinnervated free-muscle transfer to return prehensile function to an upper limb that is completely paralyzed. Although the procedure is still preliminary, a successful case is briefly described.

Adult↗

Levels of pulmonary surfactant protein A in fetal lung and amniotic fluid from protein-malnourished pregnant rats.

Surfactant protein A (SP-A) is a major apo-protein of pulmonary surfactant, which lines the alveolar walls, lowering the surface tension to prevent lung collapse. Pregnant rats were divided into two groups which received a diet with either 5% or 20% protein from gestational day 9. By a sensitive immunoassay, SP-A levels in the fetal lungs and the amniotic fluid showed a dramatic increase with advancing gestation after the initial appearance on gestational day 18 in both diet groups. Significantly lower levels of SP-A in pregnant rats fed 5% protein diet than those in pregnant rats fed 20% protein diet were observed in the fetal lungs on gestational day 21 and in the amniotic fluid on gestational days 20 and 21. The profiles of increased SP-A levels in the amniotic fluid reflected those in the fetal lungs during gestation. Immunohistochemical examination with anti-rat SP-A antibody at 21 days of gestation showed that the immunoreactive staining of bronchiolar epithelial Clara cells and alveolar type II cells were weaker in the fetal lung sections from pregnant rats fed 5% protein diet than in those from pregnant rats fed 20% protein diet. It is concluded that protein malnutrition in pregnant rats affects the biosynthesis of SP-A in the fetal lungs, which may have important consequences for prematurity and decreased respiratory functions in the neonatal lungs at birth.

Amniotic Fluid↗

[The individual difference of response to the negative side of self-enhancing presentation].

In this study, scales were developed to measure responses to negative aspects of others' and own self-enhancing presentation, and relationships among the scales and self-consciousness were examined. With factor analysis, the scale for responses to others' self-enhancing presentation was divided into three subscales: emotional, critical, and empathic. The scale for those of own self-enhancing presentation was similarly divided into three: disliking, analytical, and accepting. The scales and self-consciousness scale (translated by Sakamoto, 1989) were administered to 373 university and professional school students (204 male and 169 female). The main findings were as follows: 1) Self-disliking and analytical subjects had high public self-consciousness and social anxiety, and tended to show high emotionality toward other's self-enhancing presentation. 2) Self-accepting subjects had high public self-consciousness, and responded empathically, but not emotionally, to other's self-enhancing presentation.

Ego↗

[Renal function in children with reflux nephropathy followed up more than 10 years after disappearance of vesicoureteral reflux: usefulness of alpha 1-microglobulin as a marker to predict the prognosis of these children].

BACKGROUND: Although reflux nephropathy (RN) is one of the most important causes of renal failure in adolescence and young adulthood, we have no appropriate markers to know the future course of children with RN. In order to find out useful marker to predict the prognosis of these children, we analyzed the result of over ten years follow-up of children with RN. METHODS: We evaluated renal function in 25 patients (aged between 11 years and 23 years, 14 males and 11 females) with RN using urinary alpha 1-microglobulin (alpha 1 m), urinary albumin and 99mTc-dimercaptosuccinic acid (DMSA) renal scan. All patients were followed up more than 10 years after disappearance of vesicoureteral reflux. RESULTS: Of 25 patients, 13 showed high levels of urinary alpha 1 m (> 4.4 mg/gCr = upper normal limit) during follow-up period. Among them, renal dysfunction developed in 9 on DMSA renal scan and/or serum creatinin (Cr) level. Before puberty, all patients, even children with renal dysfunction (serum Cr > 1.0 mg/dl), remained in normal or slight high urinary albumin levels. Five cases, showed high levels of urinary alpha 1 m before puberty, demonstrated a remarkable increase of urinary albumin levels after puberty. CONCLUSION: From these results, it was suggested that urinary levels of alpha 1 m could be utilized as a marker to predict the prognosis of children with RN.

Alpha-Globulins↗

[Eighteen cases of multicystic kidney: natural history and renal function of the contralateral kidney].

PURPOSE: The objective of this study is to evaluate natural history of multicystic kidney (MCK) and renal function of the contralateral kidney. METHODS: We analyzed 18 children (7 boys and 11 girls) with unilateral MCK. The sizes of cysts were investigated by ultrasonography. Urinary beta 2-microgloblin (beta 2 m), alpha 1-microgloblin (alpha 1 m) and N-acetyl-beta-D-glucosaminidase (NAG) and albumin were determined as markers of tubular and glomerular damage. The renal function was evaluated by 99m Tc-dimercaptosuccinic acid (99 m Tc-DMSA) renal uptake rate. RESULTS: Nephrectomy was performed in 2 children. In 14 (87.5%) of 16 cases who were followed conservatively, the size of cysts was spontaneously reduced by 1-18 months (mean 6.4). Neither hypertension nor malignancy from the affected kidney has been observed in follow-up periods of 6-63 months. One patient had minor degree of contralateral ureteral dilatation which resolved spontaneously. Lower DMSA uptake rate of contralateral kidney was demonstrated in 63% (10/16). Markers of tubular damage were abnormally high in these patients. CONCLUSION: From these results, the most appropriate management of MCK is conservative with ultrasonic monitoring. Long-term follow-up testings with special care on contralateral renal function will be necessary because the overload to the contralateral healthy kidney may have already occurred during infancy and cause focal glomerulosclerosis and renal failure in future.

Aging↗

Enlarging splenic vein aneurysm associated with stagnation of splenic venous blood flow.

We report a case of splenic vein aneurysm (SVA) that was enlarged during a 17-month follow-up. A 62-yr-old female with liver cirrhosis was followed up in our hospital. Real-time ultrasonography initially detected aechoic space at the middle part of the splenic vein, confirmed as SVA by contrast-enhanced computed tomography, magnetic resonance imaging and angiography. Magnetic resonance imaging showed the stagnation of blood flow in SVA, which suggests the presence of hypertension in the portal venous system. Moreover, SVA enlarged in parallel with the development of esophageal varices. These observations suggest that the persistent stagnation of blood flow in the portal venous system may have played a major role in the increase in size of the SVA in this case.

Aneurysm↗

Homologous desensitization of thromboxane A2 receptor in 1321N1 human astrocytoma cells.

The desensitization mechanisms that regulate the response to thromboxane A2 (TXA2) were investigated in 1321N1 human astrocytoma cells. Exposure of the cells to 9,11-epithio-11, 12-methanothromboxane A2 (STA2), a stable TXA2 receptor agonist, at a concentration of 1 microM for 30 to 45 min resulted in about a 50% decrease in subsequent STA2-stimulated phosphoinositide hydrolysis and Ca2+ mobilization. However, exposure to STA2 for 0 to 5 hr did not change the binding of [3H]SQ29548, a TXA2 receptor antagonist. Because STA2-induced GTPase activation decreased and the GTP sensitivity in inhibition of [3H]SQ29548 binding by STA2 disappeared after the cells had been exposed to STA2 for 30 min, the TXA2 receptor desensitization during the short-term might result from G-protein-receptor uncoupling. STA2-induced desensitization was specific for the TXA2 receptor and homologous, because SQ29548 suppressed the desensitization and STA2 pretreatment did not affect the response to carbachol, a muscarinic cholinergic receptor agonist. Exposure to STA2 for 24 hr decreased [3H]SQ29548 binding sites to 20 to 30% of control and abolished STA2-stimulated phosphoinositide hydrolysis, indicating that long-term desensitization might induce down-regulation of the TXA2 receptor. However, exposure to STA2 for 1 to 24 hr did not change the level of TXA2 receptor mRNA. These results show that homologous desensitization of the TXA2 receptor in human astrocytoma cells can be divided into two stages; the early stage involves uncoupling of receptors from G-proteins and the late stage involves a loss of receptors in cells. The mRNA levels may not be controlled by stimulation of the TXA2 receptor.

Astrocytoma↗

The distribution of renin containing cells in scarred kidneys.

PURPOSE: To evaluate changes in renal renin synthesis secondary to renal scarring from urinary tract disease, we investigated the immunohistochemical distribution of renin in normotensive children with scarred kidneys and determined whether renal renin content correlates with the degree of interstitial fibrosis. MATERIALS AND METHODS: We performed semiquantitative analysis of the immunohistochemical distribution of renin using rabbit anti-human renin antibody in the scarred kidneys of 3 boys and 17 girls with urinary tract disease. RESULTS: Immunoreactive renin was mainly present within the afferent arteriole. Immunostaining of the juxtaglomerular apparatuses, interlobular arteries and renin containing cells increased with the degree of interstitial fibrosis. Glomeruli disjointed from proximal tubules, that is atubular glomeruli, were observed in fibrosed areas and renin was distinctly noted in the juxtaglomerular apparatus of atubular glomeruli. CONCLUSIONS: Scarred areas may be responsible for the hyperproduction of renin and angiotensin II, which in turn promotes renal scarring and an increase in atubular glomeruli. This cycle may lead to progressive renal scarring.

Adolescent↗

[Efficacy and limitation of directional coronary atherectomy for acute myocardial infarction assessed by depth of tissue resection].

The efficacy and limitations of directional coronary atherectomy (DCA) for acute myocardial infarction were evaluated in 44 patients (left anterior descending artery : 27 lesions, left circumflex artery : 2 lesions, right coronary artery : 15 lesions) who underwent DCA within 24 hours after the onset of chest pain. Thirty-two patients underwent DCA for residual stenosis of > or = 75% with TIMI flow grade II or III after thrombolysis (immediate DCA), and 12 patients underwent DCA for suboptimal results after immediate percutaneous transluminal coronary angioplasty (rescue DCA). In all patients, DCA resulted in residual stenosis of <25% (15 +/- 8%), and the primary success rate was 100%. No major complications (death, emergency bypass grafting) occurred. Repeat angiography was performed in 41 patients before discharge (2.4 +/- 0.7 weeks later) and in 39 patients during follow-up (5 +/- 2 months later). Reocclusion was not found at the follow-up. Restenosis was not found before predischarge, but was found in 19 of the 39 patients (49%) at the follow-up. Histological analysis of atheroma samples was performed to evaluate the influence of subintimal resection on restenosis. Patients were divided into two groups according to the depth of tissue resection : intimal resection and subintimal resection. The restenosis rate associated with subintimal resection was significantly higher than that associated with intimal resection (80% vs 29%, p < 0.01). DCA is useful for persistent patency of the infarct-related coronary artery in patients with acute infarction, but subintimal resection may increase the restenosis rate during the follow-up period.

Adult↗