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Biomedical subjects

K Sakamoto

Publications and source records attributed to K Sakamoto.

At least 217 records · Page 12Linked to original sources
PubMed1999

Identification of a high-copy-number plasmid suppressor of a lethal phenotype caused by mutant DnaA protein which has decreased intrinsic ATPase activity.

The induction of a mutant DnaA protein (DnaA E204Q) with decreased intrinsic ATPase activity in cells causes a lethal phenotype. Based on our results that the decreased ATPase activity of DnaA E204Q is activated to the level of a wild-type protein in the presence of partially purified stimulating factors for DnaA ATPase, we tested the hypothesis that genes encoding the stimulating factors can be cloned as high-copy-number plasmid suppressors for the lethality caused by DnaA E204Q. We isolated a number of high copy-number plasmids that suppress the lethal phenotype. The genes responsible for the suppression of the lethal phenotype were revealed to be dnaN, relA, pcnB and cyaA by subcloning, and a site-directed mutational analysis. The mechanisms by which these genes suppressed the lethal phenotype were examined in vivo and in vitro.

Adenosine Triphosphatases↗
PubMed1999

Nonpeptide arginine vasopressin antagonists for both V1A and V2 receptors: synthesis and pharmacological properties of 4'-[5-(substituted methylidene)-2,3,4,5-tetrahydro-1H-1-ben zoazepine-1-carbonyl]benzanilide and 4'-[5-(substituted methyl)-2,3-dihydro-1H-1-benzoazepine-1- carbonyl]benzanilide derivatives.

Arginine vasopressin (AVP) has a dual action, i.e. vasoconstriction and water reabsorption via V1A and V2 receptors, and may play a role in a number of diseases, including congestive heart failure (CHF), hypertension, renal disease, edema, and hyponatremia. We have attempted to develop a new series of AVP antagonists for both V1A and V2 receptors based on the hypothesis that the blockade of both V1A and V2 receptors might be beneficial to CHF patients. In this report, a series of compounds structurally related to 4'-[5-(substituted methylidene)-2,3,4,5-tetrahydro-1H-1-benzoazepine-1-carbonyl ]benzanilide (exo-olefin isomer) and 4'-[5-(substituted methyl)-2,3-dihydro-1H-1-benzoazepine-1-carbonyl]benzanilide (endo-olefin isomer) were synthesized and examined to have AVP antagonist activity for both V1A and V2 receptors. As a result, it was found that the (E)-exo-olefin isomers showed more potent binding affinity compared with endo-olefin isomers. Among these (E)-exo-olefin isomers, (E)-N-methyl-{1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahyd ro-1H-1 -benzoazepin-5-ylidene}acetamide (14) exhibited the most potent binding affinity and (E)-N-methyl-(1-{4-[2-(4-methylphenyl)benzoylamino]benzoyl}-2,3,4,5- tetrahydro-1H-1-benzoazepin-5-ylidene)acetamide (20) exhibited a high AVP antagonist activity for both V1A and V2 receptors after intravenous administration. Details of the synthesis and pharmacological properties of this series are presented.

Animals↗
PubMed1999

Treatment with l-cis diltiazem before reperfusion reduces infarct size in the ischemic rabbit heart in vivo.

l-cis Diltiazem, an optical isomer of diltiazem, protects against myocardial dysfunction in vitro, whereas its Ca2+ channel blocking activity is about 100 times less potent than that of diltiazem. However, there is no evidence that l-cis diltiazem actually protects against ischemia/reperfusion injury in vivo. To assess this, we employed an anesthetized rabbit model, where the left circumflex artery was occluded for 15 min and reperfused for 360 min. Treatment with diltiazem before and during ischemia (bolus 200 microg/kg and 15 microg/kg per minute for 25 min, i.v.; 575 microg/kg total) showed slightly depressed hemodynamic parameters, while l-cis diltiazem (1150 microg/kg) had no effect. Treatment with l-cis diltiazem produced a high recovery of the thickening fraction and limited the infarct size in a dose-dependent manner. Furthermore, the treatment with l-cis diltiazem (1150 microg/kg) or diltiazem (575 microg/kg) 5 min before reperfusion also limited the infarct size, but not after reperfusion. These results suggest that l-cis diltiazem affects some events in the onset of reperfusion, independently of Ca2+-channel-blocking action. Our observations are the first to show that l-cis diltiazem demonstrated its cardioprotective action in the ischemic rabbit heart in vivo.

Anesthesia↗
PubMed1999

Spontaneous hemothorax secondary to immature teratoma of the mediastinum.

Spontaneous hemothorax in a 20-year-old boy was caused by rupture of an immature teratoma of the mediastinum. The tumor bled spontaneously into the right pleural space. This life-threatening complication necessitated emergency surgery. The unusual cause and the interesting clinical course of spontaneous hemothorax are described.

Adult↗
PubMed1999

Evaluation of three types of blinks with the use of electro-oculogram and electromyogram.

Three kinds of blinks, spontaneous, reflex, and voluntary, were measured for 11 men using electromyogram (EMG) at the orbicularis oculi muscle on the right side and electro-oculogram (EOG) in the vertical direction to the right eyelid. The amplitude and the duration time were defined here from the raw waves of the EMG and the EOG for the three kinds of blinks. The amplitude of the EMG indicated that the mean value for the spontaneous blinks was significantly smaller than that of the voluntary blinks and the mean duration of the EMG shows the value for the spontaneous blinks was smaller than that for the reflex and the voluntary blinks. The EMG for the spontaneous blinks had a smaller amplitude and a shorter duration time than the other blinks. The EOG amplitude indicated that the mean value for the spontaneous blinks was significantly smaller than that for the voluntary blinks, but there was no significant difference between the spontaneous blinks and the other blinks for the duration of the EOG. The amplitude and the duration for both the EMG and the EOG discriminated any two types of blinks from three blinks by statistical test. Those values for the EMG and the EOG are effective indices for the evaluation of blinks. Moreover, the coefficients of variation of the amplitude and durations of EMG and EOG for three kinds of blinks denote their characteristics. Multiple discriminant analysis distinguished the types of blinks simultaneously. The resultant maximum correct rate for the three blinks reaches to be 81.8%. So far, it has been difficult to discriminate the blinks quantitatively, but the procedures presented here are able to solve the difficulty.

Adult↗
PubMed1999

A study on the effects of countermeasures for vibrating tool workers using an impact wrench.

The aims of this study were (1) to measure frequency-weighted vibration acceleration and (2) to study the effects of introducing a vibration-proof impact wrench on VWF in workers. The subject pool was 383 male workers who were regularly using an impact wrench and taking special medical examinations for vibration syndrome in a factory from 1982 to 1999. The prevalence of workers with VWF increased gradually after 1982, reached a peak value (4.8%) in 1986, gradually decreased after 1987, and disappeared in 1994. Sixteen subjects who had had VWF at least one time during the observation period were selected for this study. The stages of VWF were at stage I on the Stockholm Workshop scale in all subjects. After the vibration-proof impact wrench was introduced in 1986, the vibration acceleration of the impact wrench measured on the handle decreased from 8.6-11.1 m/s2 to 5.1-7.1 m/s2. The actual time per day that subjects were assumed to use the impact wrench was 108 minutes. The subjects actually used an impact wrench more than the occupational exposure limit allowed. However, VWF disappeared after the introduction of a vibration-proof impact wrench. This might have resulted from the combined effect of introducing the vibration-proof impact wrench and certain countermeasures that were taken against cold working environments.

Adult↗
PubMed1999

Differential kinetics of circulating angiotensin IV and II after treatment with angiotensin II type 1 receptor antagonist and their plasma levels in patients with chronic renal failure.

BACKGROUND: Angiotensin II (Ang II) C-terminal hexapeptide (referred to as Ang IV) possesses the characteristics of a real hormone with specific receptors and biological effects. Clinical application of Ang II type 1 receptor (AT1-R) antagonists cause an increase in plasma Ang II level, which may result in enhanced production of Ang IV. PATIENTS AND METHODS: In this study, we measured plasma Ang IV and Ang II levels in patients with chronic renal failure (CRF), and also examined the changes in Ang IV and Ang II levels after administration of an ATI-R antagonist. RESULTS: Ang II and Ang IV levels in CRF patients untreated with hemodialysis (n = 16) were 15.8+/-3.6 and 6.0+/-1.1 pg/ml, respectively, which did not differ significantly from Ang II (20.6+/-2.4) and Ang IV levels (8.6+/-1.1) in normal controls (n = 23). The ratio of Ang IV to Ang II was 38%, similar to that in the controls (41%). Ang II or Ang IV levels in CRF patients treated with hemodialysis (n = 12) were also similar to the control values. Ang IV levels had a significant correlation with Ang II levels (r = 0.59). When hypertensive patients were treated with an AT1-R antagonist candesartan for 7 days, Ang II and Ang IV levels were increased 5.5- and 4.1-fold relative to the control levels, respectively. Ang II levels 28 and 56 days after treatment were significantly lower than those 7 days after treatment, whereas Ang IV levels did not differ significantly from those 7 days after treatment. Similar differential kinetics in Ang II and Ang IV levels after long-term (90 days) treatment with an AT1-R antagonist was also confirmed in experiments using rats. Significant decrease in blood pressure continued during long-term treatment with an AT1-R antagonist. CONCLUSION: These findings demonstrated that plasma Ang IV levels in patients with CRF did not differ significantly from those in normal subjects, and that treatment with an AT1-R antagonist caused marked increases in both Ang II and Ang IV levels. In contrast, during long-term treatment plasma Ang II levels were more rapidly decreased than Ang IV levels, suggesting longer-lasting enhancement of the action of Ang IV rather than that of Ang II after treatment with an AT1-R antagonist.

Aged↗
PubMed1999

[Seven cases of marked pulmonary fibrosis in the upper lobe].

We report on 7 patients with marked idiopathic pulmonary fibrosis in the upper lung lobes. The patients were generally characterized by the following pathological and clinical features: (1) marked subpleural pulmonary opacities and reticular shadows mainly in the upper lobes, with a progressive reduction in lung volume; (2) nonspecific fibrosis (subpleural, zonal, rather well-defined fibrosis with small cysts and honeycomb lesions) in 5 patients and interstitial pneumonia in 2, mainly in the upper lobes; and (3) a slender build, and a family history of recurrent spontaneous pneumothorax. Clinically, all 7 cases resembled idiopathic upper-lobe fibrosis as described by Amitani in 1992. Further clinical and experimental research will be required to delineate the characteristics of idiopathic fibrosis affecting primarily the upper lobes.

Adult↗
PubMed1999

Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations.

In the present study, functional characteristics of organic cation transporter (OCTN)1, which was cloned as the pH-dependent tetraethylammonium (TEA) transporter when expressed in mammalian human embryonic kidney (HEK)293 cells, were further investigated using Xenopus oocytes as well as HEK293 cells as gene expression systems. When OCTN1-derived complementary RNA was injected into Xenopus oocytes, pH-dependent transport of [14C]TEA was observed as the same in HEK293 cells. In contrast, a replacement of sodium ions with potassium ions in the surrounding medium did not cause any change in [14C]TEA uptake in Xenopus oocytes expressed with OCTN1. In addition, when OCTN1 was expressed in HEK293 cells, efflux of TEA from the cells was pH dependent, with an accelerated rate at acidic external medium pH. Accordingly, membrane potential or sodium ions are suggested to have no influence on [14C]TEA transport and the transport activity of OCTN1 is directly affected by pH itself. Furthermore, addition of the unlabeled TEA in external medium enhanced the efflux of preloaded [14C]TEA. These observations suggest that OCTN1 is a pH-dependent and bidirectional TEA transporter. OCTN1-mediated [14C]TEA uptake was inhibited by various organic cations such as cimetidine, procainamide, pyrilamine, quinidine, quinine, and verapamil. In addition, uptakes of cationic compounds such as [3H]pyrilamine, [3H]quinidine, and [3H]verapamil and zwitterionic L-[3H]carnitine were increased by expression of OCTN1 in Xenopus oocytes. Accordingly, OCTN1 was functionally demonstrated to be a multispecific and pH-dependent organic cation transporter, which presumably functions as a proton/organic cation antiporter at the renal apical membrane and other tissues.

Animals↗
PubMed1999

Contribution of motor unit activity enhanced by acute fatigue to physiological tremor of finger.

The contribution of motor unit activity to a physiological tremor (hereafter called as tremor) in a middle finger is studied by both a power spectrum and a correlation analysis in which the correlation coefficient and the coherence spectrum are obtained when five kinds of loads, 0, 50, 100, 150, and 200 g, are added to the middle finger for two minutes in a loading experiment on twelve male subjects. A weight of 200 g is applied to the subjects for ten minutes in a fatigue experiment. Throughout both experiments, the middle finger remains stretched from the load of the weight. The tremor is measured by an accelerometer (MT-3T, Nihon Kohden, Japan) attached to the middle finger, and the surface electromyogram (EMG) is measured by bipolar electrodes placed on m. extensor digitorum communis. A power spectrum analysis is carried out on the tremor and EMG, and a correlation analysis is performed on the relationship between the tremor and the demodulated EMG. It is found in the loading experiment that when the weight on the finger increases, the amplitude of the tremor oscillation increases since the activity of the motor units of the muscle is enhanced by the phenomenon of recruitment. Two frequency components of the tremor spectra at 10 Hz and 25 Hz under a no load condition reflect the components of the activity of the motor units of the muscle because the tremor shows a significant correlation in the frequency zone of 10 Hz and 25 Hz with the demodulated EMG. The lower frequency component of the tremor spectrum at 10 Hz results in synchronized activity of the motor units, while the higher frequency at 25 Hz occurs from the stretch reflex loop via the motoneurons of the spinal cord. The shift of the higher frequency component to the lower frequency domain due to the load of the weight originates from the prolongation of the response time of the finger mechanical system because the lag time at the peak of the correlation coefficient increases with the load of the weight. It is found in the fatigue experiment that the amplitude of the tremor oscillation increases with the progress of fatigue. The increase is caused by the recruitment of the motor unit activity of the muscle holding the finger as well as by the synchronization of the firings of the motoneurons. The progress of the synchronization is verified by the fact that the mean power frequency (MPF) of the EMG spectrum decreases and the correlation between the tremor and the demodulated EMG increases with the progress of fatigue. The mechanisms of the increase of the amplitude of the tremor oscillation under the load of the weight to the finger and under the state of fatigue of the finger are elucidated by the analysis of the tremor and EMG.

Adult↗
PubMed1999

[Regrowth of bullae around the staple-line is one of the causes of postoperative recurrence in thoracoscopic surgery for spontaneous pneumothorax].

Since August 1994, we have performed 65 thoracoscopic surgeries for spontaneous pneumothorax. Our operative method is partial resection of the lung with bullae using endoscopic autosuture. Three patients underwent reoperation because of persistent air leakage in one case and postoperative recurrences in two cases. In addition, we performed a second operation in one case that had undergone thoracoscopic surgery for spontaneous pneumothorax in another hospital. At the second operation, regrowth of bullae was found at the edge of staple-line in three of the 4 cases, and in one of these cases, such regrown bullae seemed to be a cause of recurrence of pneumothorax. The regrowth of the bullae was caused by incomplete resection at the initial surgery in one case. Such incomplete resection and oversight were not noticed in the review of the videotape of the initial surgeries in two cases. Reinforcement of the staple-line is necessary for prevention of recurrence of pneumothorax.

Adolescent↗
PubMed1999

Relationship between acute insulin response and vitamin K intake in healthy young male volunteers.

To evaluate the effects of vitamin K (VK) on pancreatic function, especially on acute insulin response, 25 healthy young male volunteers were given an oral load of 75 g of glucose, and their mean daily VK intake was estimated by a one-week food check list. After excluding low (<20) and high (> or =25) body mass index (BMI) subjects, the remaining 16 participants were divided into three semi-equal groups according to VK intake. Blood VK status of the low VK intake group tended to be poorer than that of the high intake group (median of 5 samples: prothrombin time; 12.5 vs 12.2s and protein-induced VK absence-factor-II; 23 vs 15 mAU/ml), but fasting plasma glucose status was not markedly different between both groups: [plasma glucose (PG); 87 vs 86 mg/dl, immunoreactive insulin (IRI); 6.7 vs 5.3 microU/ml, HbA1c; 4.8 vs 4.9%]. However, at 30 min after glucose loading, PG of the low VK intake group tended to be higher than those of the high intake group (160 vs 145 mg/dl) and IRI was lower (36.1 vs 52.3 microU/ml). Insulinogenic index (incremental IRI/incremental PG, 0-30 min) of the low VK intake group was significantly lower than that of the high intake group (0.4 vs 0.9). These results suggested that VK may play an important role on the acute insulin response in glucose tolerance.

Adult↗
PubMed1999

[The repair of congenital coronary artery fistula in the neonatal period].

We operated on 10 cases diagnosed as congenital coronary artery fistula, including 2 critical neonates. Such neonates needed special care for perfusion pressure drop at the beginning of cardiopulmonary bypass and imperfect delivery of cardioplegia. This phenomenon is likely to depend on the shunt size of a fistula, that is much larger in such neonates than in older patients who could be operated on electively. It was helpful in the situation to crossclamp the main PA, compress the fistula and crossclamp the aorta quickly for a standstill. We prefer the closure of a fistula in the recipient chamber especially when an important area is supplied distally to the origin of the fistula. However, if a ventricle is a recipient chamber, the closure through coronary incision should be done as the neonates in our series. There were two hospital deaths due to vascular leakage syndrome and hypoxia, respectively. Aortic regurgitation (AR) got worse in two after the operation. They were found to have more dilatation and distortion in the Valsalva's sinus which appeared to affect the aortic annulus to some extent. It is likely due to long-standing larger shunt. Contrary to them, the patient operated on during neonatal period was followed by no increase of AR, though she had the largest shunt of our series. We have an impression it could be prevented by earlier operation.

Aortic Valve Insufficiency↗
PubMed1998

Antiphase circadian expression between BMAL1 and period homologue mRNA in the suprachiasmatic nucleus and peripheral tissues of rats.

BMAL1 is a putative transcription factor which is involved in circadian rhythm generation in Drosophila. Northern blot analysis was performed to investigate the expression of rat BMAL1 mRNA in the suprachiasmatic nucleus (SCN) and peripheral tissues. In the SCN, circadian expression of BMAL1 mRNA which reaches its peak level at the time of dark-light transition was observed, and the expression pattern was antiphase to those of two period (per) homologues, rPer1 and rPer2. However, no circadian oscillation for rat Clock mRNA was detected. The circadian expression of BMAL1 mRNA was also observed in peripheral tissues such as brain (excluding the SCN), eye, heart, kidney, and lung. The amplitudes of BMAL1 and rPer2 mRNA expression levels were correlated between the different tissues, suggesting that the circadian expression of BMAL1 mRNA plays an important role in generating the circadian expression of per homologue genes in mammals.

ARNTL Transcription Factors↗
PubMed1998

RNA aptamers that specifically bind to the Ras-binding domain of Raf-1.

RNA aptamers that bind to the Ras-binding domain (RBD) of a proto-oncogene product, Raf-1, were isolated from a pool of random sequences using a glutathione S-transferase-fused RBD (GST-RBD). The RNA molecules bind to the GST-RBD, but not to GST, with dissociation constants of about 300 nM. In contrast, these RNA aptamers do not bind to the Ras-binding domain of the RGL protein, which is also known to be activated by Ras. The aptamers actually compete with Ras for binding to the Raf-1 RBD. The anti-Raf-1 aptamers may be used to specifically inhibit the Ras-Raf interaction in the complicated signaling network in mammalian cells.

Base Sequence↗
PubMed1998

Structural determination of sulfated tetrasaccharides and hexasaccharides containing a rare disaccharide sequence, -3GalNAc(4,6-disulfate)beta1-4IdoAalpha1-, isolated from porcine intestinal dermatan sulfate.

In the course of structural studies on sulfated oligosaccharides isolated from porcine intestinal heparin after extensive digestion with Flavobacterium heparinase, we isolated several heparitinase-resistant unsaturated oligosaccharides. Amino sugar analysis of these oligosaccharides indicated that they contained galactosamine residues but no glucosamine residues. They were sensitive to chondroitinase ABC but resistant to chondroitinase AC-II, and therefore derived from dermatan sulfate, which was presumably contained as a minor component in the starting heparin preparation. The structures of these oligosaccharides were characterized by enzymatic digestions in conjunction with HPLC analysis of the digests and by one-dimensional and two-dimensional 500-MHz 1H-NMR spectroscopy. Structures of two tetrasaccharides and two hexasaccharides were determined as deltaHexAalpha1-3GalNAc(4S)beta1-4IdoAalpha1-3GalNAc(4S), deltaHexAalpha1-3GalNAc(4S,6S)]beta1-4IdoAalpha1-3GalNAc(4S) , deltaHexAalpha1-3GalNAc(4S)beta1-4IdoAalpha1-3GalNAc(4S)beta 1-4IdoAalpha1-3GalNAc(4S), and deltaHexAalpha1-3GalNAc(4S)beta1-4IdoAalpha1-3GalNAc(4S,6S)b eta1-4IdoAalpha1-3GalNAc(4S), where deltaHexA, IdoA, GalNAc, 4S and 6S represent 4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid, L-iduronic acid, N-acetyl-D-galactosamine, 4-O-sulfate and 6-O-sulfate, respectively. The latter three compounds have never been reported as discrete structures. Since the four isolated oligosaccharides contained an unsaturated uronic acid residue at the nonreducing terminus, they appear to have been generated by eliminative cleavage by the action of Flavobacterium chondroitinase that was probably present as a minor contaminant in the Flavobacterium heparinase preparation used. Two out of the four oligosaccharides shared the rare disulfated disaccharide sequence, -3GalNAc(4S,6S)beta1-4IdoAalpha1-. These oligosaccharides will be useful as authentic reference compounds for microanalyzing biologically active domains of dermatan sulfate.

Amino Sugars↗
PubMed1998

Familial transmission of seasonal changes in sleep and eating function in the general population.

Both genetic and environmental factors may be involved in the development of the increased sleep and appetite/body weight during winter, which are observed in seasonal affective disorder (SAD) as well as in normal variants of behavior in the general population. Decreases of these psychosomatic functions are also observed during summer, although the change may be less apparent than the winter changes. We studied familial correlation of these seasonal changes in 129 small Japanese families of the general population, using the Seasonality Pattern Assessment Questionnaire (SPAQ). No association was observed between the child and biological parents in the changes of sleep length or appetite/body weight during winter or summer. In contrast, significant spouse correlations were found in the changes of sleep and eating function during winter as well as during summer. This may indicate a role of shared environmental factors in the development of the seasonal patterns. The present results are preliminary and further studies are recommended.

Adult↗