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Biomedical subjects

C Tanaka

Publications and source records attributed to C Tanaka.

At least 343 records · Page 19Linked to original sources
PubMed1985

In vivo kinetics and thrombus accumulation of 67Ga-labeled urokinase.

Highly purified high and low molecular weight urokinase (H-UK and L-UK) were labeled with 67Ga using deferoxamine (DF) as a bifunctional chelating agent. The labeling efficiency was 91.7% for the H-UK, and 90.4% for the L-UK, respectively. The 67Ga labeled UK (67Ga-DF-UK) fully retained the enzymatic activity of the parent UK. Studies on the in vivo behavior of the 67Ga labeled UK in rabbits showed a very rapid blood clearance with half-life of 4 min (67Ga-DF-L-UK) to 8 min (67Ga-DF-H-UK). Studies carried out in rabbits with induced thrombi in the femoral vein showed thrombus-to-blood 67Ga-DF-UK activity ratios, 2h after injection, of 2.00-3.08 for the H-UK, and 0.84-1.65 for the L-UK, respectively, with thrombi aged 4 to 3 days. A dose effect of the 67Ga-DF-H-UK on its thrombus accumulation was observed. Gel chromatographic analysis of plasma samples withdrawn from those animals injected with this radiopharmaceutical revealed a reduction of the 67Ga-DF-UK effectiveness due to complexation with protein inhibitors. This led to formation of high molecular weight complexes which was reflected in the very fast blood clearance. Its implication in thrombus accumulation is discussed. In conclusion, usefulness of DF for labeling UK with 67Ga or 68Ga with no alteration of UK enzymatic properties was demonstrated. The use of 67Ga-DF-UK as a diagnostic or therapeutic radiopharmaceutical is promising.

Animals↗
PubMed1985

Observations of energy metabolism in neuroectodermal tumors using in vivo 31P-NMR.

The energy metabolism of living tumors in rats and hamsters were investigated by obtaining in vivo 31P-NMR spectra, and the effects of chemotherapy on tumors were evaluated by observing the changes of these spectra. Tumor cells of rat glioma, human glioblastoma and human neuroblastoma were inoculated subcutaneously in the lumbar region of the animals. After the tumor grew to over 1.5 cm in diameter, in vivo 31P-NMR spectrum data was obtained selectively from the tumor with a TMR-32 spectrometer (Oxford Research Systems, U.K.). Several peaks (ATP, inorganic phosphate (Pi), phosphodiesters and phosphomonoesters (PME) were observed in the tumors. The heights of these peaks varied widely corresponding to the tumor growth. However, the spectrum pattern of each tumor in an active stage was found to be essentially the same regardless of histological type or tumor origin. The phosphocreatine (PCr) peak was small, ATP and PME peaks were large and tissue pH calculated from the chemical shift of Pi was low in each tumor group. After intravenous injection of a large dose of a chemotherapeutic agent, ATP peaks decreased and the Pi peak increased gradually, resulting in a dominant Pi peak pattern after several hours in all groups. With lower drug doses, spectrum changes were temporarily seen in the tumors. These findings indicated that drugs with a high dose have a selective and a direct action on the energy metabolism of tumor tissues. In vivo 31P-NMR spectra measurement is very valuable not only to investigate the energy metabolism in tumor tissue but also to evaluate the effects of chemotherapy on the tumor.

Animals↗
PubMed1985

The effects of PGD2 and 9-deoxy-delta 9-PGD2 on colony formation of murine osteosarcoma cells.

Effects of antineoplastic prostaglandins (PG), PGD2 and 9-deoxy-delta 9-PGD2, on colony formation of cloned Dunn osteosarcoma (TA 102), normal Swiss 3T3 and V-79 cell lines were evaluated. PGD2 significantly inhibited the colony formation of TA 102 cells in a dose-dependent manner at concentrations between 0.5 and 5 micrograms/ml. The IC50 value was calculated to be 0.72 microgram/ml. A dose-dependent inhibition of TA 102 colony formation was also observed with 9-deoxy-delta 9-PGD2 between 0.01 to 1 microgram/ml, the IC50 value being 0.22 microgram/ml. These prostaglandins did not exert cytocidal effects in vitro on Swiss 3T3 cells at concentrations between 0.01 to 1 microgram/ml. The two agents had no significant cytocidal effects on V-79 cells except for 9-deoxy-delta 9-PGD2 at a concentration of 5 ug/ml. These results suggest that PGD2 and 9-deoxy-delta 9-PGD2 are considered to have cytocidal activity on Dunn osteosarcoma cells in dosages which do not affect non-malignant cells.

Animals↗
PubMed1985

In vivo studies of energy metabolism in experimental cerebral ischemia using topical magnetic resonance. Changes in 31P-nuclear magnetic resonance spectra compared with electroencephalograms and regional cerebral blood flow.

The energy state of the brain during and after transient cerebral ischemia was examined in rats by in vivo measurement of 31P-nuclear magnetic resonance (NMR) spectra using a topical magnetic resonance spectrometer. EEGs and regional CBF (rCBF) were monitored on the same ischemic models. Immediately after the induction of ischemia, the height of the ATP and phosphocreatine peaks in the spectrum began to decrease with a concurrent increase of the inorganic phosphate (Pi) peak. The calculated pH from the chemical shift of Pi decreased during ischemia. The EEG pattern became flat immediately after ischemic induction. The rCBF decreased below the sensitivity level of the measuring instrument. With 30-min ischemia, the 31P-NMR spectrum returned to a normal pattern rapidly after recirculation. However, recovery of the EEG was delayed. The rCBF after recirculation showed postischemic hyperemia followed by hypoperfusion. In cases of 120-min ischemia, none of the spectra showed recovery. Thus, we could investigate the dynamic process of pathophysiological changes occurring in the ischemic brain in vivo.

Animals↗
PubMed1985

Molecular characterization of muscarinic receptor subtypes in bovine cerebral cortex by radiation inactivation and molecular exclusion h.p.l.c.

Muscarinic receptor subtypes in bovine cerebral cortex were investigated by means of radiation inactivation and molecular exclusion high performance liquid chromatography (h.p.l.c.). The functional molecular size of the muscarinic receptor in situ was determined by the radiation inactivation method. The value for the muscarinic receptor labelled with [3H]-quinuclidinylbenzilate ([3H]-QNB) was 91,000 daltons, while that labelled with [3H]-pirenzepine [( 3H]-PZ) was 157,000 daltons. The muscarinic receptor solubilized with digitonin could be labelled with [3H]-PZ as well as with [3H]-QNB. 3-[(3-Cholamidopropyl)-dimethylammonio] - propane sulphonate (CHAPS) solubilized the muscarinic receptor labelled with [3H]-QNB but not that labelled with [3H]-PZ, in agreement with the low affinity of pirenzepine for inhibiting [3H]-QNB binding in CHAPS-solubilized preparations. The size of the muscarinic receptor in solution was estimated by molecular exclusion h.p.l.c. The digitonin-solubilized muscarinic receptor had a molecular weight of 290,000 and the [3H]-QNB and [3H]-PZ binding activities behaved identically. The CHAPS-solubilized muscarinic receptor labelled with [3H]-QNB was apparently of high molecular weight (greater than 1,000,000 Mr), indicating the formation of aggregates and/or micelles. In the presence of digitonin this form was dissociated into a lower molecular weight species (580,000 Mr). These data indicate that the ligand binding component of the muscarinic receptor species labelled by both [3H]-QNB and [3H]-PZ exists on the same receptor protein, but that the [3H]-PZ binding component in situ is probably coupled to other components in the membrane.

Animals↗
PubMed1985

Substance P provoked gamma-aminobutyric acid release from the myenteric plexus of the guinea-pig small intestine.

The release of [3H]gamma-aminobutyric acid (GABA) from the isolated small intestine of the guinea-pig pre-loaded with [3H]GABA was measured in the presence of substance P and vasoactive intestinal polypeptide (VIP). Substance P (10(-10)-10(-7) M) produced a dose-dependent increase in the fractional rate of [3H]GABA release. VIP, even at 10(-7) M, did not affect the spontaneous [3H]GABA release nor the release of [3H]GABA evoked by electrical transmural stimulation (0.5 ms, 15 V, 10 Hz for 30 s). The release of endogenous GABA from the isolated small intestine was measured in the presence of substance P (10(-9) M). After 60 min superfusion, the spontaneous release of GABA was 4.61 +/- 0.14 pmol min-1 g-1 wet wt. (n = 20). Substance P (10(-9) M) produced an approximate 2-fold spontaneous release of endogeneous GABA (8.74 +/- 0.21 pmol min-1 g-1 wet wt. (n = 10)). Perfusion with Ca-free medium containing 1 mM-EGTA and tetrodotoxin (3 X 10(-7) M) inhibited the release of endogenous GABA evoked by substance P (10(-9) M). (D-Pro2, D-Trp7,9) substance P (10(-6) M) antagonized the release of endogenous GABA evoked by substance P (10(-9) M). These results indicate that substance P induces a neuronal release of GABA through its receptor located in the guinea-pig small intestine. Substance P (10(-11)-10(-7) M) produced a dose-dependent increase in the fractional rate of [3H]acetylcholine (ACh) release from the isolated small intestine pre-loaded with [3H]choline. The release of [3H]ACh evoked by substance P (10(-9) M) was inhibited by perfusion with Ca-free medium containing 1 mM-EGTA, tetrodotoxin (3 X 10(-7) M) and (D-Pro2, D-Trp7,9)substance P (10(-6) M). Bicuculline (10(-6) M) inhibited the release of [3H]ACh evoked by substance P (10(-9) M) by 68.1 +/- 4.6% (n = 5), thereby suggesting that the substance P-evoked ACh release is partly mediated through the endogenous GABA released by substance P. These results provide evidence for the neurotransmitter role of GABA and a possible excitatory role of substance P on the GABAergic neurones in the myenteric plexus of the guinea-pig small intestine.

Acetylcholine↗
PubMed1985

Uptake and release of gamma-aminobutyric acid in guinea pig gallbladder.

The presence of gamma-aminobutyric acid (GABA)-ergic neuron in guinea pig gallbladder was investigated by measuring GABA contents and glutamate decarboxylase (GAD) activity and by demonstrating the uptake and release of [3H]GABA. GABA and GAD are both present in the gallbladder, and a positive correlation in regional distribution was observed among GABA, GAD, and the number of ganglion cells. The uptake of [3H]GABA by the gallbladder showed two saturable components; a high-affinity component (Km = 23.3 microM, Vmax = 7.63 nmol X g-1 X 10 min-1) and a low-affinity component (Km = 515 microM, Vmax = 57.1 nmol X g-1 X 10 min-1). These high-affinity and low-affinity transport systems corresponded to those obtained in the presence of beta-alanine and L-2,4-diaminobutyric acid, respectively, thereby suggesting the presence of neuronal and nonneuronal GABA transport systems in this tissue. Electrical transmural stimulation produced an increase in [3H]-GABA release from the isolated gallbladder preloaded with [3H]GABA, in the presence of beta-alanine. The stimulation-evoked release of [3H]GABA was prevented by calcium-free medium containing 1 mM EGTA and tetrodotoxin, thereby indicating that the released GABA originates from the nerve terminals. These results provide evidence for the presence of GABA-ergic neurons in the guinea pig gallbladder.

Animals↗
PubMed1985

Autoradiographic evidence for dopaminergic innervation in guinea pig spinal cord.

In studies of the localization of the dopaminergic nerve terminals in the cervical cord of guinea pig, autoradiographic analysis of the spinal cord loaded with [3H]dopamine [( 3H]DA) was done under conditions that prevented the nonspecific uptake of [3H]DA. There was specific labeling in the gray matter and a high density of [3H]DA was present in the dorsal horn (DH). Moderate labeling was observed in the neuropil in the vicinity of the central canal. There were grain concentrations in close approximation to the cell bodies of numerous neurons in the DH and to the cell bodies of a few of the motoneurons in the ventral horn (VH). These dopaminergic terminals are possibly linked to sensory transmission and somatic motor function.

Animals↗
PubMed1985

Influence of hypoxia on release and uptake of neurotransmitters in guinea pig striatal slices: dopamine and acetylcholine.

We studied the influence of hypoxia on the release of [3H]dopamine ([3H]DA) and [3H]acetylcholine ([3H]ACh), uptake of [3H]DA and [3H]choline and Ca2+-influx in guinea pig striatal slices. Tetrodotoxin (TTX)-sensitive and Ca2+-dependent electrically evoked release of [3H]DA was not affected by hypoxia, while spontaneous release of [3H]DA was rapidly increased. On the other hand, by hypoxia, the evoked [3H]ACh release gradually decreased and was diminished to about 45% 40 min later. Hypoxia suppressed the Vmax of [3H]DA uptake to one third and that of [3H]choline to half of the control values, but with no change in either of the Km values. Hypoxia reduced both the acetylation and the uptake of [3H]choline in slices preliminarily incubated with 3 mM or 25 mM K+ medium. Stimulation-induced Ca2+-influx was slightly suppressed and was 78.1% of the control values even after 40 min exposure to hypoxia. The Ca2+-dependent neurotransmitter release process itself appears to be well preserved against hypoxia as compared with the uptake process. Our findings imply that hypoxia could result in differential alterations of neural activity depending on the specific sensitivity of the presynaptic process of neurotransmission.

Acetylation↗
PubMed1985

Dopamine regulation of [3H]acetylcholine release from guinea-pig stomach.

The involvement of dopamine receptors in cholinergic transmission of guinea-pig stomach was investigated by analyzing the effects of dopamine receptor agonists and antagonists on acetylcholine (ACh) release from this organ. Electrical stimulation (1-20 Hz) of strips of guinea-pig stomach preloaded with [3H] choline induced a [3H]ACh release that was calcium dependent and tetrodotoxin sensitive. Dopamine inhibited this transmural stimulation-induced [3H]ACh release in a concentration-dependent manner (10(-8)-10(-4) M). This effect of dopamine was not altered by 10(-5) M hexamethonium, thereby suggesting that the major dopamine receptors are located on the postganglionic cholinergic neurons. Concentration-response curves for dopamine on [3H]ACh release were inhibited by haloperidol, sulpiride and domperidone but not by prazosin, yohimbine, propranolol and ketanserin. LY 171555, an agonist for the D2 dopamine receptor, but not SKF 38-393, an agonist for the D1 dopamine receptor, to some extent decreased the release of [3H]ACh induced by transmural stimulation. In view of the results, the release of ACh from postganglionic cholinergic neurons is probably required through dopamine receptors antagonized by D2 antagonists but not by adrenergic or serotonin receptor antagonists.

Acetylcholine↗
PubMed1985

[Cardiovascular hemodynamics in patients with essential hypertension during multi-stage exercise].

We investigated cardiovascular hemodynamics in patients with essential hypertension at rest and during exercise. Eight patients with borderline hypertension (Group B), 18 patients with sustained hypertension, and 10 normotensive subjects (Group N) were studied. Patients with sustained hypertension were categorized in two groups; 10 patients without cardiac hypertrophy (Group NH), and eight patients with cardiac hypertrophy (Group HH). To assess the cardiovascular hemodynamics, M-mode echocardiograms, electrocardiograms and carotid pulses were recorded during multistage exercise using a supine bicycle ergometer. Blood pressure was measured simultaneously by the cuff method. At rest, isovolumic relaxation times (IRT) in Groups NH and HH were significantly prolonged as compared with that of Group N. The IRT of Group HH was significantly prolonged as compared with that of Group NH (Group N: 0.06 +/- 0.01 sec, Group B: 0.07 +/- 0.01 sec, Group NH: 0.08 +/- 0.02 sec, Group HH: 0.09 +/- 0.01 sec, respectively). Only the atrial filling fraction of Group HH was significantly increased over that of Group N (Group N: 25.6 +/- 12.1%, Group B; 30.0 +/- 8.1%, Group NH: 27.9 +/- 11.3%, and Group HH: 41.4 +/- 13.1%, respectively). The total peripheral vascular resistance (TPR) in Groups NH and HH was significantly increased over that of Group N (Group N: 1600 +/- 224 dyne/sec/cm-5, Group B: 1704 +/- 465 dyne/sec/cm-5, Group NH: 2370 +/- 608 dyne/sec/cm-5, and Group HH: 3290 +/- 1598 dyne/sec/cm-5, respectively). There was no significant difference in the cardiac index, ejection fraction or heart rate among all groups at rest and during exercise. However, the difference between TPR at rest and TPR at a load of 75 watt (delta TPR) was increased in Groups NH and Group HH over Group N (Group N: 558 +/- 166 dyne/sec/cm-5, Group B: 614 +/- 336 dyne/sec/cm-5, Group NH: 883 +/- 415 dyne/sec/cm-5, and Group HH: 1306 +/- 774 dyne/sec/cm-5, respectively). From these findings, we concluded that there is early diastolic left ventricular dysfunction in Groups NH and HH, and that the degree is more distinct in Group HH. It seems that systolic left ventricular function of both groups is normal during moderate exercise loads, and marked reduction of the TPR in both groups during exercise may be caused by marked peripheral vascular dilatation.

Adult↗
PubMed1985

Measurements of in vivo 31P nuclear magnetic resonance spectra in neuroectodermal tumors for the evaluation of the effects of chemotherapy.

The effects of chemotherapy on living tumor tissue in hamsters and rats were investigated by measuring the 31P nuclear magnetic resonance spectra using topical magnetic resonance. Human neuroblastoma, human glioblastoma, and rat glioma tumor cells were inoculated s.c. in the lumbar region of the animals. After the diameter of the tumors increased to 1.5 cm, in vivo 31P nuclear magnetic resonance spectra were measured selectively in the tumors with a TMR-32 spectrometer. Adenosine triphosphate, inorganic phosphate (Pi), phosphodiester, and phosphomonoester peaks were observed. The phosphocreatine peak was hardly detectable, adenosine triphosphate and phosphomonoester peaks were high, and tissue pH, calculated from the chemical shift of Pi, declined. Regardless of the tumor origin or the histological type, the spectral pattern of each neuroectodermal tumor was found to be essentially the same. After i.v. injection of a large dose of a chemotherapeutic agent, adenosine triphosphate peaks decreased and Pi increased gradually, resulting in a dominant Pi peak pattern after 6 to 12 hours. However, during the same period, there were no observable changes in the spectra of normal organs. These findings indicated that the drugs have a selective and direct action on the energy metabolism of tumor cells. With lower drug doses, no remarkable changes were seen in the spectrum. Measurement of in vivo 31P nuclear magnetic resonance spectra is valuable not only to investigate the energy metabolism in tumor tissue but also to evaluate the effects of chemotherapy.

Adenosine Triphosphate↗
PubMed1984

Alpha 1- and beta-adrenergic and muscarinic cholinergic receptors in guinea-pig nasal mucosa.

The alpha 1- and beta-adrenergic and muscarinic cholinergic receptors in guinea-pig nasal mucosa were measured for the first time by direct binding techniques using [3H]prazosin, [3H]dihydroalprenolol ([3H]DHA) and [3H]quinuclidinyl benzilate ([3H]QNB). The maximum binding capacities of [3H]prazosin, [3H]DHA and [3H]QNB in guinea-pig nasal mucosa were 20.1, 42.3, 159 fmol/mg protein, respectively. The dissociation constants of [3H]prazosin, [3H]DHA and [3H]QNB in guinea-pig nasal mucosa were 0.37, 0.77 and 1.5 nM, respectively. After the removal of the superior cervical ganglion in the guinea-pig, the number of alpha 1-adrenergic receptors was increased in the nasal mucosa while the number of beta-adrenergic and muscarinic receptors remained unchanged. Thus, alpha 1-adrenergic receptors are probably postsynaptic receptors in the target cells of sympathetic nerves, while beta receptors relate to the circulating catecholamines.

Adrenergic Fibers↗
PubMed1984

Inhibitory histamine H2-receptor in the guinea-pig urinary bladder.

The histamine H2-receptor in the guinea-pig urinary bladder was characterized by determining the effects of histamine and impromidine on contractions induced by electrical transmural stimulation (ETS). The contractile responses to ETS (0.5 ms, 15 V, for 15 s) at frequencies of 1 to 30 Hz were abolished by treatment with tetrodotoxin, and were partly inhibited by scopolamine, indicating that the ETS-induced contraction has scopolamine-sensitive and -resistant components. Histamine and impromidine inhibited the scopolamine-resistant contraction induced by ETS but not the ETS-induced scopolamine-sensitive contraction and nicotine- and acetylcholine (ACh)-induced contractions. The inhibitory effects of histamine and impromidine were antagonized by cimetidine, but not by diphenhydramine and mepyramine. Thus, the inhibitory effect of histamine may be mediated through H2-receptors. As impromidine did not affect the tetrodotoxin-sensitive and Ca2+-dependent ETS-evoked release of ACh and noradrenaline (NA) from the isolated urinary bladder preloaded with [3H]choline and [3H]NA, respectively, the H2-receptor may not be involved in the cholinergic and adrenergic mechanisms. These results indicate that histamine H2-receptors are present in the guinea-pig urinary bladder. The H2-receptor located on non-cholinergic excitatory neurons may be involved in the inhibitory action produced by histamine.

Acetylcholine↗
PubMed1984

A phorbol ester and A23187 act synergistically to release acetylcholine from the guinea pig ileum.

Electrical stimulation of guinea pig ileum preloaded with [3H]choline provokes the release of [3H]acetylcholine (ACh) in a Ca2+-dependent manner. This release was markedly increased by the tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA). The combination of the ionophore A23187 and TPA produced the release of [3H]ACh up to a level equal to or exceeding a maximal response induced by electrical stimulation. A23187 alone gave only a minor response and TPA alone had no apparent effect on the [3H]ACh release. Thus, protein kinase C probably plays a role in cell surface signal transduction related to the release of transmitters from nerve endings.

Acetylcholine↗
PubMed1984

Evidence for the neurotransmitter role of norepinephrine in the ventral thalamic nucleus of the guinea pig: localization, uptake and release.

The localization, uptake and release of norepinephrine (NE) by the isolated guinea pig ventral thalamic nucleus (VT) were studied to determine the possible neurotransmitter role of this catecholamine. The NE content in the VT was 356 +/- 24 ng/g wet weight and intraneuronal localization of NE was demonstrated in the VT by histofluorescence. [3H]NE accumulation into the VT slices was about 3 times that of [3H]NE (10(-7) M) in the medium 10 min after incubation. Kinetic analyses indicated 2 components of [3H]NE accumulation, one representing a high (Km1 4 X 10(-7) M and Vmax1 1.5 pmol/mg/10 min) and a low (Km2 1.8 X 10(-6) M and Vmax2 5 pmol/mg/10 min) affinity uptake system. Desmethylimipramine (10(-5) M) reduced the high affinity uptake of [3H]NE by 30% of the control value. Electrical stimulation of the slices increased the efflux of [3H]NE from tissues preloaded with [3H]NE, in a current- and frequency-dependent fashion. The release of [3H]NE induced by stimulation of up to 1 mA was inhibited by tetrodotoxin (10(-6) M) or Ca-free medium containing EGTA (10(-4) M). These findings provide strong evidence for the neurotransmitter role of NE in the VT.

Animals↗
PubMed1984

In vivo measurement of energy metabolism and the concomitant monitoring of electroencephalogram in experimental cerebral ischemia.

The energy metabolites in rat brain in vivo were measured by using topical magnetic resonance (TMR) during the whole course of ischemia, in combination with the concomitant monitoring of electroencephalogram (EEG). Immediate loss of high energy phosphorus compounds, phosphocreatine (PCr) and ATP, resulted in the flattening of EEG after the induction of ischemia. PCr and ATP returned to almost normal level 30 min after recirculation of the ischemic brain, but EEG showed no recovery and the abnormality lasted for 12 h. The measurement of in vivo 31P-NMR is essential for the decision of the convalescence of cellular function in the brain.

Adenosine Diphosphate↗