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Biomedical subjects

F Nakamura

Publications and source records attributed to F Nakamura.

At least 127 records · Page 7Linked to original sources
PubMed1995

Angiogenic therapy of acute myocardial infarction by intrapericardial injection of basic fibroblast growth factor and heparin sulfate: an experimental study.

To examine whether angiogenesis and myocardial salvage occur, 30 micrograms basic fibroblast growth factor (bFGF) and 3 mg heparin sulfate (HS) were injected through the right atrium into the pericardial cavity by a thin needle-tipped catheter in a canine model of acute myocardial infarction. One month later infarcted weight/left ventricle weight was 24% +/- 5.2%, 25% +/- 4.0%, 18% +/- 2.4%, and 10% +/- 1.8% (mean + SE) in saline solution, HS, bFGF alone, and bFGF plus HS groups, respectively. Vascular number in the infarcted area of the outer layer was 13 +/- 3.3, 20 +/- 2.2, 47 +/- 8.3, and 136 +/- 26.3/200 x 200 microns2 in saline solution, HS, bFGF alone, and bFGF plus HS groups, respectively. Thus the vascular number was the largest in the bFGF plus HS group. The vascular number was larger in the subepicardial than in the subendocardial infarcted areas. Vessels directed from the epicardium toward the subepicardial infarcted area were also observed. The transcatheter intrapericardial injection of bFGF plus HS caused angiogenesis and myocardial salvage. This method might bring about a selective therapeutic and preventive modality of myocardial infarction irrespective of coronary anatomy and contraindications for coronary interventions and surgery.

Animals↗
PubMed1995

Observation of atherosclerotic lesions by an intravascular microscope in patients with arteriosclerosis obliterans.

The magnification power of conventional fiberscopes for intravascular use is up to x30, and therefore they are not feasible for observation of fine structures of vascular changes. We devised a microscope that enables percutaneous transluminal observation of the vascular luminal changes of cellular order. Thus we examined its feasibility in patients. The microscope was 8F in diameter with a rod lens inside, and its magnification power was from x150 to x350. The microscope was introduced into the iliac or femoral artery for observation of vascular lesions during angioplasty in seven patients with arteriosclerosis obliterans. With the aid of vital staining individually damaged endothelial cells, fibrin threads, foam cells, collagen, elastic fibers, and structure of microthrombi were discriminated clearly. The results indicate that structures of human vascular lesions of cellular order can be observed percutaneously by the intravascular microscope.

Aged↗
PubMed1995

Prediction of acute coronary syndromes by percutaneous coronary angioscopy in patients with stable angina.

To pinpoint the link between plaque characteristics and acute coronary syndromes, we performed a 12-month prospective follow-up study in 157 patients with stable angina pectoris in whom regular coronary plaques were observed by percutaneous coronary angioscopy. Acute coronary syndromes occurred more frequently in patients with yellow plaque than in those with white plaques (11 of 39 vs 4 of 118; p = 0.00021). Moreover, the syndromes occurred more frequently in patients with glistening yellow plaques than in those with nonglistening yellow plaques (9 of 13 vs 2 of 26; p = 0.00026). Thrombus arising from the ruptured identical plaques was confirmed by angioscopy as the culprit lesion of the syndromes. The results indicate that acute coronary syndromes occur frequently and in a short time in patients with glistening yellow plaques and that angioscopy but not angiography is feasible for prediction of the syndromes.

Acute Disease↗
PubMed1995

Phylogenetic place of mitochondrion-lacking protozoan, Giardia lamblia, inferred from amino acid sequences of elongation factor 2.

Partial regions of the mRNA encoding a major part of translation elongation factor 2 (EF-2) from a mitochondrion-lacking protozoan, Giardia lamblia, were amplified by polymerase chain reaction, and their primary structures were analyzed. The deduced amino acid sequence was aligned with other eukaryotic and archaebacterial EF-2's, and the phylogenetic relationships among eukaryotes were inferred by the maximum likelihood (ML) and the maximum parsimony (MP) methods. The ML analyses using six different models of amino acid substitutions and the MP analysis consistently suggest that among eukaryotic species being analyzed, G. lamblia is likely to have diverged from other higher eukaryotes on the early phase of eukaryotic evolution.

Amino Acid Sequence↗
PubMed1995

Expression of rat kallikrein and epithelial polarity in transfected Madin-Darby canine kidney cells.

Many properties of urinary kallikrein are well characterized, but the intracellular processing of prokallikrein and release by kidney cells have yet to be clarified. We report here on the synthesis of prokallikrein in Madin-Darby canine kidney (MDCK) cells transfected with rat submaxillary gland kallikrein cDNA and on its activation by MDCK cells and by an enriched liver Golgi membrane preparation. Transfected MDCK cells secreted only prokallikrein at both the apical and basolateral sides in about a 4:1 ratio, but cells transfected with kallikrein cDNA in reverse orientation or untreated cells released only traces of the enzyme. Prokallikrein, in culture medium or in homogenized MDCK cells, was fully activated by trypsin but activated only to 44% by thermolysin. Prokallikrein was synthesized and released into the medium at a high rate: the enzyme secreted by 5 x 10(6) cells in 24 hours cleaved 46 nmol/min D-Val-Leu-Arg-7-amino-4-methylcoumarin and liberated 63 ng/min bradykinin after activation. Immunocytology indicated the association of prokallikrein with the Golgi apparatus in the transfected cells. Antiserum to rat urinary kallikrein detected a single band in a Western blot of conditioned medium and also immunoprecipitated the enzyme. Aprotinin inhibited activated prokallikrein. Although MDCK cells released prokallikrein, their homogenates activated prokallikrein at both pH 5.5 and 7.5. Prokallikrein was also activated by a highly enriched liver Golgi membrane fraction and by an endoplasmic reticulum preparation, but the Golgi preparation was 38-fold more active. The activation was blocked significantly by inhibitors of serine proteases and less by cysteine protease inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Characterization of bradykinin B2 receptors in adult myocardium and neonatal rat cardiomyocytes.

Specific [125I-Tyr8]bradykinin (BK) binding was observed on myocardial membranes from adult guinea pigs, dogs, rats, and rabbits that was displaced by unlabeled BK with an IC50 between 0.1 and 30 nmol/L. In the adult guinea pig ventricular myocardium, which displays both high- and low-affinity binding, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S; 100 mumol/L) eliminated high-affinity binding and reduced total specific [2,3-prolyl-3,4-3H(N)]BK ([3H]BK) binding by > 60%. Agonist competition binding to rat myocardial membranes was characterized as being of one affinity for BK in the nanomolar range, and it was not altered by GTP gamma S. Saturation binding studies with [125I-Tyr8]BK and [3H]BK, performed on cultured neonatal rat cardiac myocytes, revealed a single class of BK binding sites with a Kd and Bmax of 0.24 +/- 0.04 nmol/L and 18.4 +/- 1.1 fmol/mg protein, respectively (approximately 1500 receptors per cell). In competitive binding assays, unlabeled BK, Hoe 140 (a specific BK B2 receptor antagonist), and des-Arg9,[Leu8]BK (a BK B1 receptor antagonist) displaced [125I-Tyr8]BK with an IC50 of 4.3, 0.041, and 307 nmol/L, respectively. In the presence of 100 mumol/L GTP gamma S, [3H]BK binding to myocyte membranes was reduced by 40%, but the IC50 did not change. Cardiac fibroblasts, evaluated in parallel to the myocytes, contain a single class of [3H]BK binding sites (248 +/- 72 fmol/mg) with a 130-fold lower relative affinity (32.4 +/- 11.3 nmol/L) than that determined in rat cardiomyocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Local delivery of heparin inhibits neointimal hyperplasia in injured rabbit artery.

The efficacy of local delivery of an antithrombotic drug on neointimal hyperplasia was investigated in 17 rabbits. One rabbit iliac artery was injured by a balloon catheter as a control injured artery. The other iliac artery was also injured and treated by local delivery of 25 U/kg of heparin. One hour after the balloon injury, angioscopy demonstrated an occlusive or mural thrombus in all the controls, but few in the locally-treated arteries. Four weeks after balloon injury, the percent stenosis was 34 +/- 31% in the heparin treated group (n = 7, p < 0.005) vs control side 73 +/- 17%). Accumulation of FITC-labeled heparin at the injured site was confirmed by microscopy. The activated partial thromboplastin time and fibrinogen level did not change significantly. PDGF-B chain was prominent at the neointimal layer in all the controls, whereas it was less in the locally treated arteries. Thus local delivery of heparin can inhibit neointimal hyperplasia after balloon injury by reducing thrombus-related growth stimulation.

Angioscopy↗
PubMed1995

[The practical benefits of magnetoencephalography in comparison with electroencephalography in a patient with epilepsia partialis continua].

A concurrent recording of electroencephalography (EEG), magnetoencephalography (MEG) and electromyography (EMG) was carried out in a patient with epilepsia partialis continua. He had continuous clonic jerks in his right hand and fingers. The EMG electrodes were placed on the thumb of his right hand. We observed numerous MEG spikes in the left central region and about half of them were accompanied by EMG potentials with a latency of about 20 msec. The EEG spikes appeared less frequently, had low amplitudes, and had unclear morphologies and further, no clear association with EMG potentials. MEG spikes were more reliably associated with individual jerks, exemplified by EMG potentials, than the EEG spikes. The MEG spikes were sharper than EEG spikes and were about 20 msec wide. The intracranial dipole localization of the MEG spikes was estimated by overlaying the calculated generator sites on magnetic resonance images. It was found that the spikes converged along a line, presumably the central sulcus. The practical benefits of the MEG as a diagnostic tool in epilepsy are illustrated.

Adult↗
PubMed1994

Analysis of aldosine, an amino acid derived from aldol crosslink of elastin and collagen by high-performance liquid chromatography.

An ion-paired high-performance liquid chromatographic method for the determination of aldosine, which is derived from the aldol crosslink of both elastin and collagen, is described. Aldosine was determined as the pyridine derivative 6-(3-pyridyl) piperidine-2-carboxylic acid, which was synthesized by oxidative decarboxylation of aldosine using iron(III). This method does not require radioisotopes to label the aldol crosslink. In addition, pyridinium crosslinks such as desmosines can also be measured.

Amino Acids↗
PubMed1994

Effects of exogenously applied calponin on Ca(2+)-regulated force in skinned smooth muscle of the rabbit mesenteric artery.

To help elucidate the physiological role of calponin (a thin-filament-linked regulatory protein) in smooth muscle contraction, the effects of its exogenous application were investigated on actin-activated MgAT-Pase activity in crude actomyosin from chicken gizzard, and on contraction induced by Ca(2+)-dependent and -independent means in arterial smooth muscle strips skinned by saponin or beta-escin. Calponin concentration dependently inhibited actin-activated MgATPase activity with a proportional increase in its binding to actomyosin and also attenuated Ca(2+)-induced contractions, in the presence or absence of calmodulin, in skinned arterial strips. Calponin, when phosphorylated by protein kinase C, reduced both its ability to bind to actomyosin and its inhibitory action on actomyosin MgATPase. The phosphorylated calponin also had no effect on the maximum Ca(2+)-induced contraction in skinned smooth muscle, suggesting that these actions of calponin are not nonspecific. Calponin attenuated the Ca(2+)-independent contraction observed in myosin light chain thio-phosphorylated strips, or on application of trypsin-treated myosin light chain kinase. However, calponin had no effect on maintained rigor contraction. These results suggest that in vascular smooth muscle, calponin may play a physiological role in the inhibition of Ca(2+)-regulated force, possibly through a direct action on active actin-myosin interactions.

Adenosine Triphosphate↗
PubMed1994

Bromide, in the therapeutic concentration, enhances GABA-activated currents in cultured neurons of rat cerebral cortex.

We investigated the effect of bromide on gamma-aminobutyric acid (GABA)-activated currents in cultured cerebral neurons of the rat, employing whole-cell voltage- and current-clamp techniques. Application of 100 microM GABA elicited currents whose reversal potential was 0 mV with equal concentrations of chloride in both pipette and bath solutions and more negative than -60 mV with 159 mM chloride extracellularly and 4 mM chloride inside. Bicuculline blocked the currents. These findings showed that the currents were composed of chloride flux through GABAA receptor-coupled channels. Reversal potential revealed a permeability ratio of bromide with respect to chloride (PBr/PCl) of 1.51. When 100 microM GABA was applied with the extracellular solution containing 140 mM bromide and 19 mM chloride, the currents were enhanced 2.00- and 1.91-fold at the holding potentials of -20 mV and 0 mV, respectively. Extracellular solutions containing various concentrations of bromide substituted for the same amount of chloride were applied with 100 microM GABA. The therapeutic concentration of 10 mM and 20 mM bromide enhanced the currents 1.28- and 1.36-fold of the control currents at the holding potential of -20 mV, respectively. Under current-clamp recording, a larger hyperpolarization was obtained by the application of GABA with a 140 mM bromide-containing solution. These findings suggest that bromide potentiated GABA-activated currents at the therapeutic concentrations ranging from 10 mM to 20 mM, causing the larger GABA-induced hyperpolarization. It is postulated that the antiepileptic effect of bromide might occur through the potentiation of inhibitory postsynaptic potentials elicited by GABA.

Animals↗
PubMed1994

Protein phylogeny gives a robust estimation for early divergences of eukaryotes: phylogenetic place of a mitochondria-lacking protozoan, Giardia lamblia.

A partial nucleotide sequence of the mRNA encoding a major part of elongation factor 1 alpha (EF1 alpha) from a mitochondria-lacking protozoan, Giardia lamblia, was reported, and the phylogenetic relationship among lower eukaryotes was inferred by the maximum-likelihood and maximum-parsimony methods of protein phylogeny. Both the methods consistently demonstrated that, G. lamblia among the four protozoan species being analyzed, is the earliest offshoot of the eukaryotic tree. Although the Giardia EF1 alpha gene showed an extremely high G+C content as compared with those of other protozoa, it was concentrated only at the third codon positions, resulting in no remarkable differences of amino acid frequencies vis-à-vis those of other species. This clearly suggests (a) that the amino acid frequencies of conservative proteins are free from the drastic bias of genome G+C content, which is a serious problem in the widely used tree of ribosomal RNA, and (b) that protein phylogeny gives a robust estimation for the early divergences in the evolution of eukaryotes.

Amino Acid Sequence↗
PubMed1994

Percutaneous angioscopy in patients with restenosis after excimer laser coronary angioplasty.

Coronary angioscopy was performed in two patients with restenosis after excimer laser coronary angioplasty to improve our knowledge of restenosis after excimer laser angioplasty. The characteristics of the angioscopic findings in restenosis after excimer laser angioplasty consisted of smooth white plaques, which were distinctly different from the yellow plaques commonly observed in primary lesions. These findings indicate that restenosis in these patients after excimer laser angioplasty may be associated with smooth muscle cell proliferation and fibrosis.

Angioplasty, Laser↗
PubMed1994

Antithrombin and thrombolytic effects of a new antithrombin agent: angioscopic and angiographic comparison with heparin or batroxobin.

The antithrombotic effect of three different types of antithrombotic agents (antithrombin:argatroban, heparin, defibrinogenating agent:batroxobin) were evaluated in canine coronary and iliac arteries. An occlusive thrombus was produced by balloon injury. One of the three agents was infused intravenously at 1 hour after thrombus formation (heparin 250 U/kg, argatroban 0.5 mg/kg, batroxobin 0.5 U/kg) and the effect of thrombus size reduction was evaluated. On the contralateral side of the iliac artery, the preventive effect of these agents on thrombus formation was evaluated after balloon injury. In the iliac artery, angioscopic percent area obstruction by the thrombus before and 60 minutes after treatment reduced from 69% to 32% in the argatroban group, and from 64% to 51% in the batroxobin group (P < 0.0001 and P < 0.05, respectively). No significant change was observed in the heparin group. Angiography demonstrated the same trend. The percent area stenosis with thrombus at 60 minutes following balloon injury was 0.75% in the argatroban group, 18.9% in the heparin group (P < 0.05 vs argatroban), and 12.9% in the batroxobin group. Thrombus size at the treated site was smaller than that at the control site in all three groups (P < 0.05 vs control). In the coronary artery, angioscopic percent area obstruction by the thrombus before and 60 minutes after treatment reduced from 84% to 53% in the argatroban group, and from 86% to 68% in the batroxobin group (P < 0.0001 and P < 0.05, respectively). No significant change was observed in the heparin group. Angiography also demonstrated the same trend. The activated partial thromboplastin time (APTT) was prolonged to 189% of the control value with argatroban and to 1253% of the value with heparin (P < 0.0001). Fibrinogen was markedly reduced with batroxobin. These results showed that both the antithrombin agent and the defibrinogenating agent have a preventive effect on thrombus formation and the effect on thrombus size reduction, without marked prolongation of the APTT.

Angiography↗
PubMed1994

Chronic administration of angiotensin II receptor antagonist, TCV-116, in cardiomyopathic hamsters.

We examined whether specific blockade of the renin-angiotensin system is beneficial for the treatment of cardiac dysfunction in heart failure. The angiotensin II type-1 (AT1) receptor antagonist TCV-116 (10 mg.kg-1.day-1) or its vehicle was given orally to UM-X 7.1 cardiomyopathic (CM) and normal Golden Syrian (GS) hamsters for 8 wk. Plasma and cardiac angiotensin II levels were significantly higher in CM than in GS hamsters. The CM heart showed a smaller response of left ventricular (LV) pressure and first derivative of maximal LV pressure (+dP/dtmax) to the elevation of perfusion pressure (from 60 to 120 cmH2O) in Langendorff-perfused than in GS heart. Treatment with TCV-116 did not affect LV function in GS but significantly improved cardiac contractility in CM hamsters. These results suggest that the renin-angiotensin system plays an important role in the development of cardiac dysfunction due to cardiomyopathy. Blockade of this system by the AT1 antagonist TCV-116 appears to be useful in the prevention of heart failure.

Angiotensin II↗