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Biomedical subjects

M Nakatani

Publications and source records attributed to M Nakatani.

At least 37 records · Page 2Linked to original sources

Effect of non-selective endothelin blockade, TAK-044, on the ischemic cellular injury of rat heart.

The aim of this study is to evaluate the role of non-selective endothelin blockade (TAK-044) in ischemic myocardial injury. Forty anesthetized rats were separated into four groups: 1) TAK-I group, after preinjection of TAK-044 (3 mg/kg), LAD was ligated for 60 min and reperfused for 60 min; 2) Saline (SAL)-I group, LAD ligation and reperfusion without TAK-044; 3) TAK-C group, sham operated TAK group; 4) SAL-C group, sham-operated SAL group. Myocardium from each group was separated and analyzed by biochemical and ultrastructural procedures. Reperfusion arrhythmia (VT) was observed in 88% of the SAL-I group, in contrast to only 36% of the TAK-I group. At the end of reperfusion, hemodynamics indicated no significant differences between these two groups. The Ca(++)-ATPase activity of sarcoplasmic reticulum (SR) was 3.9 mumoles Pi/mg protein/h (39% of SAL-C group) in the SAL-I group, while that in the TAK-I group was significantly higher at 6.1 (54%). The ratio of infarct/risk area was 58% in the SAL-I group and 36% in the TAK-I group. In the ultrastructural observations, irreversibly injured cells of the ischemic portion were reduced significantly from 35% (SAL-I group) to 14% (TAK-I group). Thus, our results indicated that endothelin blockade reduced ischemic cellular injury. The mechanism of this reduction was speculated to be a resistance to ischemic injury in the subcellular levels of the myocardium conferred by a reduction of vascular constriction and improvement of imbalance in the energy supply and demand.

Animals↗

The role of ATP-sensitive potassium channels in the mechanism of ischemic preconditioning.

We clarified the role of K(ATP) channels in the mechanism of ischemic preconditioning by using K(ATP) channel opener, nicorandil, and K(ATP) channel inhibitor, glibenclamide. Forty anesthetized dogs were divided into five groups: (a) control (C), (b) ischemic preconditioning (PC), (c) intravenous infusion of nicorandil before PC (Ni), (d) glibenclamide pretreated with PC (Gl + PC), and (e) glibenclamide pretreated with Ni (Gl + Ni). All groups were followed by 60-min ischemia and 60-min reperfusion and analyzed by the biochemical procedures. At the end of 60-min reperfusion, percentage of segment shortening in C indicated paradoxic bulging. This value was significantly recovered in PC and Ni, but it was still negative in Gl + PC and Gl + Ni. Ca2+ -adenosine triphosphatase (ATPase) activity of sarcoplasmic reticulum (SR) was significantly decreased in C. In PC and Ni, this activity was significantly maintained; however, in Gl + PC and Gl + Ni, it was similar to that in C. State III respiration of mitochondria showed similarity to the changes in SR. These results indicated that the K(ATP) channel opener enhanced the effects of ischemic preconditioning, and its blockade abolished these phenomena. We conclude that the ATP-sensitive potassium channel may play one of key roles in the mechanisms of ischemic preconditioning in the dog model.

Adenosine Triphosphatases↗

Competitive adsorption between phospholipid and plasma protein on a phospholipid polymer surface.

The competitive adsorption of proteins and phospholipids on omega-methacryloyloxyalkyl phosphorylcholine (MAPC) polymer was evaluated in this study. Albumin, fibrinogen, and dimyrstoyl phosphatidylcholine (DMPC) were used as model components. The amount of DMPC adsorbed on the MAPC polymers increased with an increase in the MAPC unit composition of the polymer. The methylene chain length of the MAPC unit was another factor influencing the DMPC adsorption when the MAPC unit composition of the MAPC polymer was low. The state of albumin and DMPC liposome adsorbed on the 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer was determined by dynamic contact angle (DCA) measurement. The adsorption strength of albumin on the MPC polymer was weaker than that on the poly[n-butyl methacrylate (BMA)], that is, the albumin was detached from the MPC polymer during the rinsing process. On the poly(BMA) surface, no difference in the shape of the DCA loops before and after contact with the DMPC liposomal suspension was observed. Fibrinogen adsorption on the MAPC polymer was detected by gold-colloid labeled immunoassay. The amount of fibrinogen adsorbed on every MAPC polymer surface was reduced by addition of the DMPC liposome in the fibrinogen solution. The number of platelets adhered on the MAPC polymer was also decreased when the DMPC liposome was present in the fibrinogen solution during pretreatment. We concluded that phospholipids were preferentially adsorbed on the MAPC polymer surface compared with plasma protein and that the adsorbed phospholipids played an important role in showing an excellent blood compatibility on the MAPC polymer.

Adsorption↗

[Effects of low dose pimobendan in patients with cor-pulmonale].

The acute and chronic efficacy of low dose pimobendan (1.25 mg x 2/day) was evluated in patients with cor-pulmonale. Fifteen patients (12 men, 3 women, mean age 73 +/- 5 yr) with right ventricular dysfunction judged by Tei's Doppler index (> or = 0.4) and poor working capacity (exercise tolerance: 2.2-6.6 MET) were studied. Mean pulmonary artery pressure, cardiac output, total pulmonary resistance using Swan-Ganz catheter, and arterial oxygen and carbon dioxide pressure (PaO2, PaCO2) were measured before and 24 hr after pimobendan administration. Maximal oxygen intake (MET), saturation of arterial blood oxygen at rest and desaturation by treadmill stress test were measured before and 1 month after pimobendan administration. Pulmonary artery pressure decreased (17.6 +/- 4.7 to 10.2 +/- 2.3 mmHg, p < 0.001) and cardiac output increased (3.5 +/- 0.6 to 5.1 +/- 0.9 l/min, p < 0.001), resulting in decreased total pulmonary resistance (5.0 +/- 1.3 to 2.1 +/- 0.7 U, p < 0.001), and a mild decrease in PaO2 (74 +/- 8 to 70 +/- 10 mmHg, p < 0.05). Exercise tolerance improved significantly (4.8 +/- 1.7 to 6.8 +/- 2.2 MET, p < 0.001), without deterioration of PaO2 and desaturation. These results indicate that low dose pimobendan is useful for the treatment of patients with cor-pulmonale.

Aged↗

[Possibility of discharge and need for rehabilitation of psychiatric patients hospitalized for one year or more in Japan: a preliminary report. Committee on Rehabilitation Affairs, Subcommittee of Survey on Rehabilitation Need].

A total of 19,342 psychiatric patients staying in a total of 143 hospitals in Japan for one year or more entered in this study in order to determine the possibility of discharge (POD) and the need for rehabilitation. Those who were assessed by the psychiatrist in charge to have POD provided community support was assured accounted for 32.5%. As for the levels of daily life functions measured with the GAF score, those assessed to have POD showed the maximum frequency between scores 51 and 60, while the others, who were not considered suitable for discharge, showed the maximum frequency between scores 21 and 30. On the other hand, the control group, consisting of subjects with psychiatric disabilities and living in the community while using day care or rehabilitation facilities, showed the maximum frequency of GAF scores between 51 and 60. Two-thirds of the study subjects were older than fifty, while in the control group those aged between 30 and 49 accounted for 49.0%, thus indicating that the residents of mental hospitals tend to be older. More than 60% of the study subjects had been staying in hospital for five years or more. Those without their own home accounted for about 60%.

Adult↗

Roles of conserved arginine residues in the metal-tetracycline/H+ antiporter of Escherichia coli.

Seven arginine residues are conserved in all the tetracycline/H+ antiporters of Gram-negative bacteria. Four (Arg67, -70, -71, and -127) of them are located in the putative cytoplasmic loop regions and three (Arg31, -101, and -238) in the putative periplasmic loop regions [Eckert, B., and Beck, C. F. (1989) J. Biol. Chem. 264, 11663-11670]. These arginine residues were replaced by alanine, lysine, or cysteine one by one through site-directed mutagenesis. None of the mutants showed significant alteration of the protein expression level. The mutants resulting in the replacement of Arg31, Arg67, Arg71, and Arg238 with either Ala, Cys, or Lys retained tetracycline resistance levels comparable to that of the wild type. Among them, only the Arg238 --> Ala mutant showed very low transport activity in everted membrane vesicles, probably due to the instability of the mutant protein. The replacement of Arg70 and Arg127 with Ala or Cys resulted in a drastic decrease in the drug resistance and almost complete loss of the transport activity, while the Lys replacement mutants retained significant resistance and transport activity, indicating that the positively charged side chains at these positions conferred the transport function. On the other hand, neither the Ala, Cys, nor Lys replacement mutant of Arg101 exhibited any drug resistance or transport activity. As for the reactivity of the Cys replacement mutants, only two (Arg71 --> Cys and Arg101 --> Cys) were not reactive with NEM, the other five mutants being highly or moderately reactive. The reactivity of the cysteine-scanning mutants around Arg101 with NEM revealed that Arg101 is located in transmembrane helix IV. It is not likely that Arg101 confers the protein folding through a salt bridge with a transmembrane acidic residue because no double mutants involving Arg101 --> Ala and the replacement of one of three transmembrane acidic residues (Asp15, Asp84, and Asp285) showed the recovery of any tetracycline resistance or transport activity. The effect of tetracycline on the [14C]NEM binding to the combined mutants S65C/R101A and L97C/R101A suggests that Arg101 may cause a substrate-induced conformational change of the putative exit gate of TetA(B).

Amino Acid Sequence↗

Which vertebrae should be assessed in diagnosing osteoporosis by plain radiography? Comparative study of radiographic findings and bone mineral density measured by dual energy X-ray absorptiometry.

In 1990, the Ministry of Health and Welfare of Japan advocated a criterion for the diagnosis radiographic bone atrophy in lumbar vertebrae. We carried out a comparative study of this criterion (i.e. , radiographic bone atrophy grading) and bone mineral density measured by posteroanterior and lateral dual energy X-ray absorptiometry. We investigated the second to fourth lumbar vertebrae of 47 postmenopausal women (mean age, 67.2 years; range, 57-82 years), to determine which vertebra would most accurately indicate osteoporosis. A significant difference in bone mineral density (P < 0.01) was found between each grade of radiographic bone atrophy in all of the second, third, and fourth vertebrae examined. The highest correlation (r = 0.714) was found between the radiographic grades and the bone mineral density on lateral dual energy X-ray absorptiometry of the third lumbar vertebrae. Our visual determinations were dependable, radiographic and a examination of the third lumbar vertebra rather than that of other lumbar vertebrae was more helpful for the detection of radiographic bone atrophy. Plain radiographic film can provide a rough estimation of bone atrophy.

Absorptiometry, Photon↗

New adsorption column (Lixelle) to eliminate beta2-microglobulin for direct hemoperfusion.

The Lixelle column is an adsorbent column used to eliminate beta2-microglobulin (beta2M) selectively from circulating blood of dialysis related amyloidosis (DRA) patients, which is used in combination with a dialyzer in series. The column has such a high capacity for adsorbing beta2M that the most intensive removal of beta2M has been possible. In clinical trials of the column, the obvious improvement of subjective symptoms such as decreases in the frequency of nocturnal awakening, the joint pain severity index, and the joint mobility index were observed. Hypotension has been the most frequent adverse event observed during treatment since the column was put on the market. It is very important to clarify the causes of both the efficacy and the side effects. A controlled prospective study is now in progress to clarify the efficacy more scientifically. The results will be published soon elsewhere.

Amyloidosis↗

On the treatment of recurrent tonsillitis by vaccination.

This paper reports on the experience of using vaccination in the treatment of recurrent tonsillitis. All of the 82 patients, who were aged between 5 and 67 years and who suffered from recurrent tonsillitis, were given an injection of a bacterial vaccine (Broncasma Berna, Swiss Serum Institute, Berne) that has been used in many countries for three decades. A dose of 0.05 ml was given once every 4 to 14 days (average once a week) on 3 to 20 occasions (average 8). The treatment prevented 75 of the 82 patients (91%) from having attacks of recurrent tonsillitis for extended periods. These 75 patients included three who relapsed into recurrent tonsillitis in spite of having tonsillectomies. As the dose used was relatively small, none of the patients complained of spontaneous pain or fever although three complained of slight tenderness at the injection point on the following day. The effect on recurrent tonsillitis of the Paspat intracutaneous injection (Luitpold Werk, Munich) has also been investigated recently. It was effective in two patients who did not respond to Broncasma Berna. In this retrospective study, low doses of bacterial vaccine reduced the incidence of recurrent tonsillitis and were well tolerated.

Adolescent↗

Biochemical and ultrastructural evaluations of the effect of ischemic preconditioning on ischemic myocardial injury--role of the adenosine triphosphate-sensitive potassium channel.

The aim of this study was to clarify the role of the adenosine triphosphate (ATP)-sensitive potassium channel on the mechanism of ischemic preconditioning (IP). Thirty-five anesthetized dogs were divided into 5 groups: (1) Control (C), (2) IP, (3) intravenous infusion of nicorandil (Ni) prior to IP, (4) glibenclamide (G1) pretreated with IP (G1+IP), and (5) G1 pretreated with Ni (G1+Ni). All groups had 60 min ischemia followed by 60 min reperfusion, and were analyzed by biochemical and morphological procedures. At the end of the 60-min reperfusion, %segment shortening in C indicated paradoxical bulging. This value had significantly recovered in IP and Ni groups, but it was still negative in the G1+IP and G1+Ni groups. Ca++-ATPase activity of the sarcoplasmic reticulum (SR) was significantly decreased in C. In the IP and Ni groups, this activity was significantly maintained; however, in the G1+IP and G1+Ni groups it was similar to that in C. State 3 respiration of mitochondria showed similar changes in the SR. In the ultrastructural observations, severely damaged cells were not observed in the IP and Ni groups. These results indicated that an ATP-sensitive potassium channel opener enhanced the effects of IP and its blockade abolished these phenomena. It was conclude that the ATP-sensitive potassium channel may play a key role in the mechanism of IP.

Adenosine Triphosphate↗

Developmentally regulated release of intraretinal neurotrophic factors in vitro.

The effects of conditioned media either from aggregates or from explants of embryonic chick retinae and of recombinant neurotrophins were tested upon the survival in vitro of ganglion cells in dissociated cell cultures from the retina of newborn rats. Ganglion cells were identified by the detection of retrogradely transported horseradish peroxidase injected bilaterally into the superior colliculus. Conditioned media increased significantly the survival of ganglion cells after 2 days in culture, at a wide range of plating densities, and had no effect upon adhesion of rat retinal cells. Media conditioned by cell ensembles from chick retinae from embryonic day 8 (E8) to E16 had neurotrophic effects. Release of neurotrophic activity peaked at E10 E12, irrespective of the numbers of cells or total concentration of protein in the conditioned media. The active molecules were non-dialyzable and were released either in the presence or in the absence of fetal calf serum. The neurotrophic activity was abolished by trypsinization, and recovered by salting-out with 25 75% ammonium sulfate. NT-4, BDNF and, to a lesser extent, NT-3, increased the survival of ganglion cells in our assay, while NGF had no effect. The data show that chick retinal cells release soluble trophic proteins according to a developmentally regulated pattern. These neurotrophic factors may be involved in local competitive interactions that help control naturally occurring neuron death among ganglion cells of the vertebrate retina.

Animals↗

Acute hemodynamic deterioration during rapid atrial pacing in patients with hypertrophic cardiomyopathy.

BACKGROUND AND HYPOTHESIS: Supraventricular tachycardia and ventricular tachycardia are often observed in patients with hypertrophic cardiomyopathy (HCM) and they often alter the clinical features of HCM. We examine the influence of supraventricular tachycardia on cardiac function and assess the clinical characteristics of patients with HCM. METHODS: We studied 32 patients with HCM and 8 normal volunteers using echocardiography under transesophageal rapid atrial pacing. RESULTS: Presyncope-associated hypotension was observed during rapid atrial pacing in 8 HCM patients, but in none of the normal controls. During rapid atrial pacing (144 +/- 8 beats/min in HCM, 146 +/- 5 beats/min in controls), systolic blood pressure (SBP), the product of left ventricular filling volume (FV) and heart rate, and fractional shortening (%FS) in the HCM patients decreased significantly compared with the basal values (138 +/- 19 mmHg vs. 99 +/- 24 mmHg, 5.0 +/- 1.2 l/min vs. 2.9 +/- 0.9 l/min, 41.7 +/- 6.2% vs. 35.2 +/- 6.0%, respectively), but these decreases were not observed in normal controls. The decrement of SBP during rapid atrial pacing in HCM patients with a history of syncope was more marked than that in those without such history. The decrement correlated positively with the indices of left ventricular hypertrophy (maximal wall thickness and wall thickness index) and with %FS, and correlated negatively with the endsystolic left ventricular diameter at rest. CONCLUSIONS: In some patients with HCM, supraventricular tachycardia causes marked hemodynamic deterioration that may be related to a history of syncope, marked hypertrophy, hyperkinesis, small cavity size, and small filling volume of the left ventricle.

Adult↗

Effect of temperature and viscosity of sieving medium on electrophoretic behavior of sodium dodecyl sulfate-proteins on capillary electrophoresis in presence of pullulan.

Pullulan was used as a sieving medium in high-performance capillary gel electrophoresis to study the effect of temperature and viscosity on electrophoretic behavior of sodium dodecyl sulfate (SDS)-proteins with molecular masses in the range of 14,400-116,000 Da. The migration time decreased with increasing capillary temperature. Equations were derived relating mobility of SDS-proteins to capillary temperature and viscosity of pullulan solution. Linear relationships were obtained from experiments between logarithm of mobility and reciprocal temperature and between double logarithmic values of mobility and viscosity of pullulan solution. The experimental results agree well with the equations.

Electrophoresis, Capillary↗

Separation mechanism of pullulan solution-filled capillary electrophoresis of sodium dodecyl sulfate-proteins.

The separation mechanism of capillary electrophoresis of sodium dodecyl sulfate (SDS)-proteins using pullulan with a molecular mass range of 50,000-100,000 as a separation matrix was investigated. The pullulan solution was filled into fused-silica capillaries whose inner walls were coated with linear polyacrylamide through chemically stable Si-C linkages. Baseline separations of SDS proteins were achieved at concentrations ranging from 3-10% w/v of pullulan. The entanglement threshold of pullulan solution was found to be around 0.5% w/v, indicating migration of SDS-proteins through an entangled pullulan network. Ferguson plots exhibited a linear relationship between log mobility and pullulan concentration. Linear relationships were also obtained for double logarithmic plots of the electrophoretic mobility and protein molecular mass. These results show that the separation is based on mass discrimination in accordance with the Ogston theory.

Electrophoresis, Capillary↗

Mitochondrial respiratory impairment in streptozotocin-induced diabetic rat heart.

The purpose of this study was to examine mitochondrial respiratory impairment in the diabetic heart. Diabetes mellitus was induced in male Wistar rats by intravenous injection of streptozotocin (STZ) for 2 to 16 weeks (Group D). In some of the diabetic rats, insulin was injected for 2 or 3 weeks prior to sacrifice (Group I). Fasting blood glucose was markedly elevated to greater than 300 mg/dl in Group D and was similar to normal glucose levels in Group I. At 2 weeks after STZ injection, state 3 was only 59.1% of that in the control. Complex I and complex V activities were also significantly reduced to 43.4% and 71.7% of those in the control, respectively. These reductions recovered with insulin treatment. This phenomenon persisted for 16 weeks. Morphological studies revealed swelling of the mitochondria and an increase in lipid droplets in diabetic cardiomyocytes, and these were also improved with insulin treatment. We conclude that in the diabetic heart, disturbance of energy production in cardiac mitochondria is generated by the impairment of oxidative phosphorylation due to depression of complex I and complex V. These changes may contribute the cardiac dysfunction that is a complication of diabetes mellitus.

Animals↗