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Biomedical subjects

F Nakamura

Publications and source records attributed to F Nakamura.

At least 145 records · Page 8Linked to original sources
PubMed1994

Physical dependence produced by dihydroetorphine in mice.

Using various administration schedules, the physical dependence produced by dihydroetorphine (DHE) was compared with that of morphine in mice. Physical dependence, evaluated by naloxone-precipitated withdrawal signs, did not develop following daily treatment with DHE (10, 20, 100 and 1000 micrograms/kg, i.p. or 30, 100 and 1000 ng/mouse, i.c.v.) for 6 d. However, 5 repeated injections of DHE (10 micrograms/kg, i.p.) at 1 or 2 h intervals did produce physical dependence and the dependent state disappeared after 2 h. Accordingly, it was demonstrated that a sufficient degree of antinociceptive activity needed to be maintained, longer than several hours, for the development of physical dependence on DHE and that the duration of the dependent state was very short. In the single dose suppression test, a single dose of DHE completely suppressed the natural withdrawal signs that appeared following abstinence in morphine-dependent animals without reappearance of significant withdrawal signs, indicating the suitability of DHE as a substitute for morphine. The characteristic properties of DHE, the extremely potent antinociceptive effect and minimal dependence, indicate the separation of the antinociceptive effect from dependence, and suggest that it may be possible to develop a novel drug which may be safely used in clinical situations.

Analgesics↗
PubMed1994

The effects of dobutamine, propranolol and nitroglycerin on an experimental canine model of congestive heart failure.

A new experimental model of acute congestive heart failure was established in open-chest dogs, and it was employed to examine the effects of dobutamine, propranolol and nitroglycerin. The model was induced by intracoronary administration of saponin, volume loading and intravenous infusion of methoxamine. Left ventricular end-diastolic pressure (LVEDP) increased from 7.9 +/- 0.6 to 24.2 +/- 1.4 mmHg, and aortic blood flow (AoF) decreased from 0.89 +/- 0.06 to 0.53 +/- 0.04 l/min. Systemic vascular resistance (SVR) increased from 9618 +/- 585 to 16492 +/- 1213 dynes.sec/cm5 and right atrial pressure (RAP) increased from 2.5 +/- 0.2 to 4.2 +/- 0.4 mmHg. Furthermore, Vmax decreased from 71.6 +/- 5.1 to 45.8 +/- 2.9 1/sec, and the time constant of left ventricular pressure decay (T) increased from 40.0 +/- 2.6 to 90.2 +/- 7.9 msec. These hemodynamic changes were stable for up to 80 min. Dobutamine improved cardiac function by increasing Vmax and by decreasing T. Consequently, dobutamine increased AoF and decreased LVEDP, while there was no change in SVR. Nitroglycerin reduced LVEDP, SVR and T; increased AoF; and did not change Vmax. Propranolol produced no improvement in the hemodynamics or cardiac function. These results indicate that the present congestive heart failure model is characterized by global left ventricular dysfunction with lowered cardiac output and increased peripheral vascular tone, and it is beneficial for evaluating the pharmacological properties of drugs for acute congestive heart failure.

Analysis of Variance↗
PubMed1994

Differential regulation of brain angiotensin II in genetically hypertensive and normotensive rats after nephrectomy.

To investigate the role of tissue angiotensin II (Ang II) in the maintenance of hypertension after nephrectomy in spontaneously hypertensive rats (SHR), Ang II levels were measured in various tissues of both 12-week-old SHR and normotensive control, Wistar-Kyoto rats (WKY), 48 h after nephrectomy or sham operation. Ang II was determined by radioimmunoassay coupled with high performance liquid chromatography. Nephrectomy caused a decrease of plasma renin activity and plasma Ang II concentration in both SHR and WKY. Aortic Ang II levels were significantly lowered by nephrectomy only in WKY, and not in SHR. Ang II levels in hypothalamic block, brainstem and cerebellum of SHR increased after nephrectomy, whereas those of WKY were unchanged. Intracerebroventricular administration of ceronapril, an angiotensin converting enzyme inhibitor, significantly decreased sustained high blood pressure in SHR 48 h after nephrectomy compared with vehicle administration, whereas intravenous administration had no effect. These results suggest that in spite of the important role of the renal renin-angiotensin system in maintenance of high blood pressure in SHR, control mechanisms may switch to other systems after nephrectomy, and that the increased brain Ang II levels after nephrectomy may be related to these mechanisms.

Angiotensin II↗
PubMed1994

[Expression of preprodynorphin mRNA in the spinal cord after inflammatory abdominal stimulation in rats].

Dynorphin, an opioid peptide, is thought to play an important role in the modulation of nociceptive neural networks at the level of the spinal cord. Fos protein is involved in the transcriptional regulation of the dynorphin gene. Although several studies have been carried out on dynorphin gene expression by noxious somatic stimuli, few have evaluated the effect of noxious visceral stimuli on the expression of dynorphin gene. In the present studies we analysed the expression of the dynorphin gene mediated by a noxious visceral stimulus in a rat model by exposure of abdominal tissue to carrageenan. Expression of preprodynorphin and c-fos mRNAs in the spinal cord neuron was examined using ribonuclease protection assays. After inflammation, a rapid increase in the levels of c-fos mRNA in the thoracic spinal cord was observed. c-fos mRNA levels rose within 30 minutes after injection, and remained elevated for 1 hour, subsequently falling to control levels. In contrast, preprodynorphin mRNA began to increase from 30 minutes after injection and remained elevated for at least 2 days. In situ hybridization with alpha 35S-labeled cRNA probe demonstrated that in the lower thoracic spinal cord preprodynorphin mRNA was expressed in dorsal horn neurons. In celiac ganglia, both preprodynorphin and c-fos mRNAs were not detected. In the peripancreatic abdominal tissue, there was acute severe inflammation consisting of necrosis and marked polymorphonuclear leucocytic infiltration. These data demonstrate that after abdominal tissue inflammation, activation of dynorphin biosynthesis occurred in thoracic spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1993

Enhancement of monosynaptic excitatory postsynaptic potentials by glutamate in frog spinal motoneurons.

We analyzed glutamate-induced enhancement of the amplitude of monosynaptic excitatory postsynaptic potentials evoked by stimulation of the lateral column fibers (LC-EPSPs) on lumbar motoneurons in the frog spinal cord. Low concentrations (0.1-0.3 mM) of glutamate, which produced small depolarization, often enhanced EPSP associated with inhibition of a paired pulse facilitation and increased occurrence of spontaneous EPSPs. With 1 mM glutamate, transient enhancement of EPSP was seen in some cells during the early phase or prior to large depolarization, even when input conductance was increased. Transient or sustained enhancement of EPSP was occasionally seen with N-methyl-D-aspartate, kainate and quisqualate, but not with L-2-amino-4-phosphonobutyrate. The results suggest that glutamate enhanced release of excitatory transmitters at low concentrations that apparently did not affect the postsynaptic membrane.

Animals↗
PubMed1993

Calponin phosphatase from smooth muscle: a possible role of type 1 protein phosphatase in smooth muscle relaxation.

Smooth muscle myosin bound phosphatase (MBP) purified from chicken gizzard, which is a holoenzyme of type 1 delta protein phosphatase and dephosphorylated intact myosin, catalyzed the dephosphorylation of calponin phosphorylated by protein kinase C (PK-C). The Km of MBP for calponin was 0.6 microM and the Vmax was 350 nmol/min/mg. All of the multiple sites of phosphorylation by PK-C of calponin were completely dephosphorylated by MBP. Functionally, calponin dephosphorylated by MBP recovered its inhibitory effect on the actin-activated Mg(2+)-ATPase activity of myosin. Therefore, these results suggest that a type 1 delta protein phosphatase causes relaxation of smooth muscle by the dephosphorylation not only of myosin but also of calponin.

Animals↗
PubMed1993

Identification of the regulatory site in smooth muscle calponin that is phosphorylated by protein kinase C.

F-actin and tropomyosin inhibited the phosphorylation of calponin by protein kinase C, and the phosphorylation reduced the binding of calponin to F-actin and tropomyosin. Labeled phosphate from [gamma-32P]ATP was retained both on the chymotryptic NH2-terminal 22-kDa fragment, which contains the actin-, tropomyosin-, and calmodulin-binding regions, and on the COOH-terminal 12-kDa fragment. Fractionation of tryptic 32P-labeled peptides by high performance liquid chromatography allowed isolation of three phosphopeptides (designated T1, T2, and T3), each of which was located in three repeating amino acid motifs of calponin. Both the relative initial rates and extent of phosphorylation decreased in the order T2 > T3 > T1. Both serine and threonine residues were phosphorylated in T1 (GASQAGMTAPGTK), and only a threonine residue was phosphorylated in T2 (FASQQGMTAYGTR) and in T3 (GASQQGMTVYGLPR). As the 22-kDa fragment contained only T2, the phosphorylation site in T2 appeared to regulate the binding of calponin to F-actin and tropomyosin. The amino acid sequence of T2 indicates that protein kinase C phosphorylates Thr184. Thus Thr184 is the preferred site of phosphorylation and is functionally the most important of the sites phosphorylated by protein kinase C in smooth muscle calponin.

Actins↗
PubMed1993

Acute response of the arterial wall to pulsed laser irradiation.

This study was designed to examine the acute response of normal arterial wall to pulsed laser irradiation. Irradiation with an Excimer or a Holmium YAG laser was performed in 15 normal iliac sites of 8 male New Zealand white rabbits. The excimer laser was operated at 308 nm, 25 Hz, 50 mJ/mm2/pulse, and 135 nsec/pulse and the Ho:YAG laser was operated at 2.1 microns, 3.5 Hz, 400 mJ/pulse, 250 microseconds/pulse. The excimer and Ho:YAG laser were coupled into a multifiber wire-guided catheter of 1.4 and 1.5 mm diameter, respectively. The mean luminal diameter increased similarly from 2.01 +/- 0.29 to 2.46 +/- 0.27 mm (P < 0.0005) and from 2.09 +/- 0.53 to 2.45 +/- 0.30 mm (P < 0.005) after excimer and Ho:YAG laser irradiation, respectively. Perforation occurred in 3 of 15 Ho:YAG irradiated sites and 0 of 15 excimer laser irradiated sites. The sites irradiated with excimer or Ho:YAG laser had similar histologic features, consisting of shedding of the endothelium, disorganization of internal elastic lamina, localized necrosis of vascular smooth muscle cells, and fissures in the medial layer. However, the sites irradiated with excimer laser had lower grading scores than those irradiated with the Ho:YAG laser (P < 0.05). Irradiation with excimer or Ho:YAG laser of normal arteries results in: (1) vasodilation of the irradiated artery; (2) localized mechanical vascular injury, and (3) Ho:YAG laser induces more severe damage to the arterial wall than excimer.

Angioplasty, Laser↗
PubMed1993

Pleomorphic carcinoma of the pancreas with osteoclast-like giant cells.

We studied two cases of pleomorphic carcinoma of the pancreas with osteoclast-like giant cells. The cut surface of both tumors was firm and whitish-tan in color, with extensive hemorrhage and necrosis. Microscopically, these tumors were composed mainly of pleomorphic mononuclear cells and numerous bizarre giant cells, with a spindle-cell sarcomatoid appearance and adenocarcinomatous elements exhibiting varying degrees of differentiation. Multinucleated giant cells resembling osteoclasts were frequently located around sites of necrotic hemorrhage. Immunohistochemically, most tumor cells of sarcomatous areas and some anaplastic giant cells were positive for vimentin and cytokeratin. Both carcinoembryonic antigen and CA 19-9 were detected in tumor cells in one case, forming ducts or glands. These findings suggest that the tumors in these two cases originated from pancreatic-duct cells with mesenchymal differentiation. In contrast, osteoclast-like giant cells in both cases showed strong immunoreactivity with vimentin and with KP1 and PG-M1 (CD68), which are monoclonal antibodies that react with a histiocyte-macrophage-associated antigen; however, there was no reaction with any epithelial markers. Thus, osteoclast-like giant cells are not epithelial in nature, suggesting that their origin of histiocyte-macrophage lineage is possibly induced as a paraneoplastic product.

Aged↗
PubMed1993

Excimer and holmium yttrium aluminum garnet laser coronary angioplasty.

Recently access to the coronary arteries became available to laser angioplasty because of a new technique utilizes a pulsed laser source and multifiber, "over-the-wire" guided catheters. The aim of this study was to evaluate the early and long-term results and the side effects of coronary angioplasty with an excimer or a Ho-YAG laser. Forty consecutive patients were treated with the Ho-YAG laser (group I) and 46 consecutive patients were treated with the excimer laser (group II). The primary laser angioplasty success rate was 55% and 72% (NS) for groups I and II, respectively. This success rate was highest in saphenous vein grafts. It was similar in calcified and noncalcified lesions and in total occlusions and stenoses. It tended to be lower in long lesions than in short ones (40% vs 60%; p < 0.05 and 44% vs 78%; NS for groups I and II, respectively). Laser stand-alone therapy was performed in 5% of patients in group I compared with 22% in group II (p < 0.05). Failures were due to the inability of the laser catheter tip to reach the lesion, to cross the obstruction, or to obtain a significant reduction in stenosis. They were more frequent in patients in group I than in those in group II (45% vs 28%). There were no deaths, no myocardial infarctions, and no need for emergency coronary artery bypass grafting because most patients had total occlusions or a well-protected coronary artery. Complications included acute closure in 8% of patients in group I and in 17% of patients in group II and spasm in 10% and 13% of patients in groups I and II, respectively. Dissection occurred more frequently in patients in group II than in those in group I (28% vs 7%; p < 0.04). The angiographic patency rate at 6-month follow-up was 33% and 29% for patients groups I and II, respectively. Multifiber, wire-guided catheters provide easy access to the coronary arteries. Excimer laser angioplasty is effective but induces a high rate of dissections. Technical improvements are required to ablate more tissue to possibly reduce the restenosis rate. Further studies are needed to elucidate the mechanism of side effects and to reduce the restenosis rate.

Adult↗
PubMed1993

Reconsideration of the effects of selfing on the viability of Hymenolepis nana.

A single cysticercoid of Hymenolepis nana was orally administered to an SPF-ICR strain mouse which was congenitally free of H. nana. Gravid proglottids of the resulting adult worm (parental generation) were fed to flour beetles, Tribolium confusum. Six or 14 days later, one cysticercoid from the beetles was fed to each mouse. Gravid proglottids were subsequently recovered and fed to beetles as above. This procedure was repeated for more than 20 generations. H. nana can survive repeated selfing and has been maintained for at least 27 generations. No decrease in the proportion of cysticercoids into adults with repeated selfing was observed in our experiments. Our results appear to conflict somewhat with results reported previously. This discrepancy may be due to a difference in mice used as experimental hosts, although some other causal factors, e.g. fluctuation of infective rate or difference in the varieties of H. nana strain used cannot be excluded.

Animals↗
PubMed1993

Discrepancy between renin mRNA and plasma renin level in angiotensin-converting enzyme inhibitor-treated rats.

1. To investigate the role of transcriptional and post-transcriptional factors in increasing renin synthesis secondary to angiotensin-converting enzyme (ACE) inhibitors, we studied the changes in levels of renal renin mRNA, plasma renin and other hormonal factors. 2. Spontaneously hypertensive rats were orally administered 10 mg/kg spirapril or vehicle daily for 3, 14 or 28 days. 3. Plasma renin activity in the spirapril-treated group was significantly elevated compared with that in the vehicle group at any time (P < 0.01). However, there was no significant change in plasma angiotensin II concentration between the two groups. The ratio of renal renin mRNA to beta-actin mRNA in the spirapril-treated group was higher than that in the control group (P < 0.01). 4. At 28 days, plasma renin activity in the spirapril-treated group was significantly elevated compared with that at 14 days (P < 0.05). However, there was no change in renin mRNA between 14 and 28 days after ACE inhibitor administration. 5. Plasma ACE activity in the treatment group was less than that in the control group at any time (P < 0.01). 6. Our study demonstrated a non-proportional change in plasma renin and renal renin mRNA levels. It is suggested that the main determinant of the rate of renin synthesis after administration of an ACE inhibitor may be post-transcriptional factors, and that unknown mechanisms may be involved in the increase in plasma renin level after long-term administration of ACE inhibitor in addition to the short feedback mechanism brought about by the decrease in angiotensin II.

Actins↗
PubMed1993

The angiotensin-converting enzyme inhibitor, perindopril, prevents cardiac hypertrophy in low-renin hypertensive rats.

1. To examine whether an angiotensin-converting enzyme (ACE) inhibitor prevents left ventricular (LV) hypertrophy even in low-renin hypertension, we studied the effect of the administration of perindopril on cardiac hypertrophy induced by partial renal ablation in hypertensive rats. 2. Rats that had undergone partial nephrectomy were randomly divided into four groups that received the following as drinking water: Group A, tap water; Group B, 1% sodium chloride (NaCl); Group C, NaCl + perindopril 3 mg/kg per day; and Group D, NaCl + perindopril 1 mg/kg per day. Plasma renin activity (PRA), angiotensin-II (AII) concentration and cardiac tissue AII were measured. 3. Supplementation of NaCl following nephrectomy increased the blood pressure and cardiac weight compared with rats that had undergone nephrectomy alone (P < 0.05). Treatment with perindopril (3 mg/kg per day) did not affect the blood pressure and plasma AII but inhibited the increase of cardiac weight (P < 0.05). Left ventricular AII was decreased in cases of reduced renal mass hypertension, but was not changed by treatment with perindopril. 4. These results demonstrate that perindopril may be able to prevent LV hypertrophy even in low-renin hypertension, which was not mediated by a reduction of blood pressure or suppression of the circulating and cardiac renin-angiotensin systems. Other mechanisms of ACE inhibitors may contribute to the cardioprotective effects.

Angiotensin II↗
PubMed1993

Reduction of vasoreactivity and thrombogenicity with laser-thermal angioplasty: comparison with balloon angioplasty.

UNLABELLED: The vasoreactivity and thrombogenicity of laser-thermal angioplasty were examined and compared with those of balloon angioplasty in an atherosclerotic rabbit iliac artery. Eight rabbits underwent laser-thermal angioplasty with a 1.7-mm hot-tip probe activated at 7 W with a probe temperature of 126 +/- 19 degrees C in one iliac artery. The other iliac artery was treated with balloon angioplasty using a 2.0-mm balloon. Angiographic luminal diameter increased from 0.19 +/- 0.15 to 1.54 +/- 0.35 mm by laser and from 0.29 +/- 0.22 to 1.84 +/- 0.20 mm by balloon (P less than 0.0001, respectively). However, it decreased to 1.34 +/- 0.42 for laser and 0.45 +/- 0.39 for balloon 60 minutes later (P less than 0.0001 vs immediately post). Both iliac arteries were visualized using angioscopy, which revealed thrombotic obstruction of 91% stenosis in the ballooned artery and 8% stenosis in the lased artery. Vasoreactivity of treated vessels was also investigated. Segments 3-mm long were obtained from either treated artery or control artery and examined for noradrenaline (10 -7 M) contraction. The segments were then mounted isometrically with 1 g tension in Krebs-bicarbonate buffer. Developed tension was 0.13 +/- 0.21 g for laser thermal and 2.33 +/- 0.4 g for its control (P less than 0.0001), and 0.15 +/- 0.16 g for balloon dilatation and 2.12 +/- 0.43 g for its control (P less than 0.0001). Neither acetylcholine at 10 -6 M or papaverine at 10 -4 M induced relaxation of treated segments. Histology showed slight thermal injury at thermally-treated sites without thrombus, and intimal and medial dissection with thrombus formation at balloon dilated site. IN CONCLUSION: (1) neither a laser-thermal recanalized or a balloon dilated obstructed artery is vasoreactive to constrictive or relaxant agents; and (2) laser-thermal angioplasty results in less thrombogenicity than balloon angioplasty under moderate probe temperature.

Angioplasty, Balloon, Coronary↗
PubMed1993

Role of tissue renin angiotensin system in two-kidney, one-clip hypertensive rats.

To investigate the molecular pathology of two-kidney, one-clip (2K-1C) rats, we examined the gene expressions of the renin-angiotensin system (RAS) and angiotensin II (ANG II) concentration in various tissues in the early (4 wk) and chronic (16 wk) phases of hypertension. Four weeks after clipping, the brain renin mRNA level was lower in 2K-1C rats than in control rats (P < 0.05). On the other hand, the levels of brain and renal angiotensinogen mRNA were not significantly different in the two groups. The brain and adrenal ANG II concentrations were significantly higher in 2K-1C rats than in control rats. Sixteen weeks after clipping, there was no significant difference in the brain renin mRNA levels in the two groups, and renal and brain angiotensinogen mRNA levels were normal. Moreover, the ANG II concentrations in the adrenals and brain (except the cortex) of 2K-1C rats were not significantly higher than those in control rats. These results show a differential pattern of tissue RAS gene expression in rats during the development of 2K-1C hypertension, which is regulated in a tissue-specific manner. Furthermore, the data suggest that brain ANG II may be affected by circulating ANG II, but not by the brain renin angiotensin system, and may regulate brain renin, probably by negative feedback through its own receptor.

Actins↗
PubMed1993

Role of angiotensin II in high fructose-induced left ventricular hypertrophy in rats.

Recent studies suggest the linkage of hypertension and insulin resistance. High fructose diet is known to induce hyperinsulinemia and hypertension in rats. In a previous study, however, high fructose (66%) diet failed to elevate blood pressure but increased left ventricular weight in Sprague-Dawley rats. In the present study, we investigated the precise mechanism of high fructose diet-induced changes in the cardiovascular system in rats. Intake of fructose-enriched diet for 2 weeks increased serum insulin and plasma angiotensin II levels. Urinary excretion of sodium and norepinephrine was not changed. Blood pressure measured directly through an indwelling catheter was not increased, but left ventricular weight and protein content were increased by high fructose diet. To further elucidate the role of the renin-angiotensin system, an angiotensin II type 1 receptor antagonist, TCV-116, was given orally at 1 mg/kg per day with either normal or high fructose diet. Concomitant administration of TCV-116 did not affect plasma glucose or serum insulin levels. Plasma angiotensin II was increased, but neither urinary sodium nor norepinephrine was changed by TCV-116. TCV-116 similarly decreased blood pressure in rats on normal and high fructose diets. Increase in left ventricular weight induced by high fructose diet was prevented by the concomitant administration of TCV-116. On the other hand, left ventricular weight in control rats was not changed by TCV-116. In conclusion, increased plasma angiotensin II may account for the left ventricular hypertrophy induced by high fructose diet, whereas hemodynamic change, sodium retention, and the sympathetic nervous system do not play an important role.

Angiotensin II↗