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Biomedical subjects

T Kumazawa

Publications and source records attributed to T Kumazawa.

At least 253 records · Page 14Linked to original sources

Functional and metabolic effects of propafenone in the rat heart-lung preparation.

The effects of propafenone on cardiac function and myocardial metabolism were assessed in the isolated rat heart-lung preparation. Propafenone 0.3, 3 or 30 microg.ml(-1) was administered 5 min after the start of perfusion. Heart rate decreased in the 30 microg.ml(-1) group significantly following the drug administration. The highest dose of propafenone (30 microg.ml(-1)) reduced cardiac output significantly, and this dose was associated with a higher incidence of arrhythmias than the other groups. Although there were no significant differences in myocardial lactate and glycogen concentrations among groups, ATP content in the 30 microg.ml(-1) group was significantly less than that in the control group. As therapeutic plasma concentration of propafenone is about 0.6 (range 0.06 to 1.0) microg.ml(-1), 30 microg.ml(-1) is 50 times greater than its concentration. These results suggest that the negative inotropic and chronotropic effects of propafenone are almost same with those of lidocaine which we have previously reported.

Journal Article↗

Failure to verify high activities of polyamine oxidase in pregnancy serum.

The activity of polyamine oxidase in human pregnancy serum was measured by our new specific method with radioisotopic N1-acetylspermine as substrate. The activity in pregnancy serum was very low and did not increase during gestation; it was not higher than that in nonpregnancy serum. The high polyamine oxidase activities previously reported by others appear to result from contamination with diamine oxidase, the level of which is high in pregnancy serum.

Brain↗

Canine taste nerve responses to umami substances.

The taste responses to the "umami substances" such as monosodium glutamate (MSG), guanosine 5'-monophosphate (GMP) and inosine 5'-monophosphate (IMP) were recorded from the canine chorda tympani nerve. A large synergism was observed between MSG and the nucleotides in most mongrel dogs (type A dog). The extent of the synergism between MSG and the nucleotides was much larger than that observed in any other animal examined except for humans. No synergism was observed between the nucleotide (GMP) and stimuli other than MSG, such as NaCl, HCl, sucrose, quinine, and glycine. It was concluded that the dog is a suitable experimental animal for studies on the responses to umami substances. In order to differentiate umami and salt components in the responses to umami substances, effects of amiloride on the responses were examined. Amiloride inhibited the response to MSG, but did not inhibit the response to GMP alone or those induced by synergism between GMP and MSG. The present results favor a conclusion that GMP acts as an agonist and MSG acts as a modulator for the umami receptor in the dog. The synergism can be explained by an allosteric model where the umami receptor is assumed to have two binding sites, one for GMP and another for MSG.

Amiloride↗

Transduction mechanisms for the taste of amino acids.

Amino acids are important taste stimuli for a variety of animals. One animal model, the channel catfish, I. punctatus, possesses sensitive taste receptor systems for several amino acids. Neurophysiological and biochemical receptor binding studies suggest the presence of at least three receptor pathways: one is a relatively nonspecific site(s) responsive to short-chain neutral amino acids such as L-alanine (L-ALA); another is responsive to the basic amino acid L-arginine (L-ARG); still another is a low affinity site for L-proline (L-PRO). Several possible transduction pathways are available in the taste system of this animal model for these amino acids. One of these, formation of inositol trisphosphate (IP3) and cyclic AMP (cAMP), is mediated by GTP-binding regulatory proteins, while another involves ion channels directly activated by stimuli. L-ALA is a potent stimulus to cAMP and IP3 accumulation, while L-ARG at low concentrations is without effect. On the other hand, L-ARG and L-PRO, but not L-ALA, are able to activate stimulus-specific and cation-selective channels in taste epithelial membranes reconstituted in phospholipid bilayers at the tips of patch pipettes. Preliminary studies using mouse taste tissue demonstrate that monosodium-L-glutamate (MSG) did not enhance production of IP3 or cAMP. However, in reconstitution experiments using taste epithelium of mouse, conductance changes due to MSG are observed. The specificity of this channel(s) and its uniqueness have yet to be determined.

Amino Acids↗

Positive and negative ion mass spectrometry and rapid isolation with Sep-Pak C18 cartridges of ten local anaesthetics.

The positive ion electron impact (PIEI), positive ion chemical ionization (PICI) and negative ion chemical ionization (NICI) mass spectra and a rapid isolation procedure using Sep-Pak C18 cartridges are presented for ten local anaesthetics. In the PIEI mode, molecular peaks were very small or missing for most compounds. Peaks at m/z 86 due to the diethylaminoethyl or propylaminoethyl group constituted base peaks in six compounds. In the PICI mode, peaks due to M + H and M + C2H5 appeared. The cation at m/z 86 was also observed for the six compounds. This ion seems useful for the screening of local anaesthetics. In the NICI mode, anions at m/z M - H constituted base peaks for all compounds, peaks at m/z M + 12 appeared in many compounds. The total ion current in the PIEI and PICI modes generally gave higher sensitivity than in the NICI mode. Local anaesthetics present in whole blood or cerebrospinal fluid (CSF) could be rapidly isolated by use of Sep-Pak C18 cartridges with chloroform/methanol as an elution solvent. Their detection was possible using wide-bore capillary gas chromatography with SPB-1 and HP-17 wide-bore capillary columns with satisfactory separation from impurities.

Anesthetics, Local↗

Sensation of ear fullness caused by eustachian tube dysfunctions.

One hundred and ninety-four patients with a sensation of ear fullness were examined with the audiometry, tympanometry, and tubotympanoaero-dynamic graphy (TTAG) as a eustachian tube ventilatory test. In 74 cases of 194, the eustachian tube dysfunction was thought to cause an ear fullness sensation and patulous tube was found in 19 patients which is more frequent than expected. Functional unbalance of the both eustachian tubes which results from minimum ventilatory disturbance on the complaining side was also thought to be one of the causes of this symptom. The eustachian tube dysfunctions like stenotic or patulous tube could not be fully diagnosed by the audiometry and tympanometry because most patients with the eustachian tube dysfunctions showed normal middle ear pressure measured by the tympanometry. From our study, it could be concluded that eustachian ventilatory test like TTAG was very available in the patient with an ear fullness feeling which is one of the most common symptoms in the otolaryngological field.

Acoustic Impedance Tests↗

Calcium distribution and mobilization in single rat parotid acinar cells investigated by digital imaging microscopy.

The intracellular distribution and mobilization of cytosolic free calcium in single rat parotid acinar cells was analyzed by a digital imaging microscope equipped with a microspectrofluorometer, using calcium-sensitive dye fura-2. In the resting state, intracellular distribution of cytosolic free calcium concentration ([Ca2+]i) was heterogeneous: [Ca2+]i in the nuclear and perinuclear region was usually higher than that in the cytoplasm. By Ca(2+)-ionophore ionomycin and muscarinic agonist carbachol stimulation in the presence of 1 mM extracellular Ca2+, [Ca2+]i increased markedly and the gradient of [Ca2+]i between the nuclear region and the cytoplasm decreased. In ionomycin stimulation, [Ca2+]i increased homogeneously and this homogeneous increase was irreversible. In carbachol stimulation the gradient of [Ca2+]i between the nuclear region and the cytoplasm obviously reappeared within 2 min. By carbachol stimulation in the absence of extracellular Ca2+ (added 1 mM EGTA), [Ca2+]i returned to the prestimulation level after the initial transient increase. The distribution of [Ca2+]i also returned approximately to the prestimulation state. The gradient of [Ca2+]i between the nuclear region and the cytoplasm did not disappear even when [Ca2+]i elevated at the peak value.

Animals↗

Detection of immunoglobulin G antibodies to cholesterol in antisera to mycoplasmas.

Antisera were produced by inoculation of mycoplasma cells grown in PPLO broth supplemented with rabbit serum alone or rabbit serum plus Freund complete or incomplete adjuvant. By using an enzyme-linked immunosorbent assay, immunoglobulin G antibodies to cholesterol were detected in antisera to mycoplasmas (Mycoplasma salivarium ATCC 23064, M. orale ATCC 15539, M. buccale IID 802, M. faucium IID 996, and M. hominis IID 801) and rabbit serum.

Animals↗

Sensitizing effects of bradykinin on the heat responses of the visceral nociceptor.

1. Whether bradykinin (BK), which is known as an endogenous pain-producing substance, induces augmentation of the discharges of polymodal receptors evoked by heat stimulation was investigated in in vitro canine testis-superior spermatic nerve preparations. 2. The heat response was significantly augmented by pretreatments with BK at concentrations greater than 0.094 nM, whereas BK induced significant increases in the mean discharge rates at concentrations above 9.4 nM. Both effects increased in a concentration-dependent manner. The augmenting effect of BK on the heat response diminished within 10 min after application of BK, regardless of concentration. 3. When 9.4 nM BK was applied in a mixture with 940 nM NPC349, a B2 receptor antagonist, the averaged mean discharge rate evoked by BK and the averaged augmenting effect were both significantly suppressed compared with those induced by BK given alone. 4. The augmenting effect of BK on the heat response of polymodal receptors could be observed even in the absence of BK-evoked discharges per se in several cases in which low concentrations of BK or BK plus B2 antagonists were given. 5. These findings suggest that the augmenting effects of BK on the heat response depend on B2 receptor-mediated intracellular processes acting in parallel to, but not directly on, the impulse-generation mechanism of the heat response of the polymodal receptor.

Analgesics↗

Positive and negative DC potential in the vestibular system of pigeons.

DC potential in the ampulla of pigeons was studied using a glass microelectrode. After the extirpation of the cochlear duct no change in the DC potential was found. A reduction of the negative DC potential due to anoxia (anoxia-sensitive negative potential, ASNP) was found in the ethacrynic acid (EA)-intoxicated ear, while this finding was minimal or absent in the ouabain-intoxicated ear. The perilymphatic perfusion with K(+)-substituted Ringer's solution resulted in a rapid reduction of the negativity due to EA or ouabain. These findings indicate that the positive DC potential in the ampulla seems to be produced by itself and K+ diffusion potential is the main source of negative DC potential. ASNP may be the unique potential in the EA-intoxicated ear in warm-blooded animals.

Animals↗

Isolation of and calcium mobilization in vestibular hair cells of the guinea pig.

Vestibular hair cells were isolated from the macula utriculi, macula sacculi and crista ampullaris of the guinea pig, using enzymatic and mechanical techniques. The cells could be classified into two types: flask-shaped ones with a neck and rod- or round-shaped ones without a neck. The flask-shaped cells were thought to be type I cells, the rod-shaped cells type II cells, while the round-shaped cells could have been type I or type II cells. The intracellular free calcium ion concentrations [( Ca2+]i) of these cells were determined using the Ca2(+)-sensitive dye Fura-2 and digital imaging miroscopy. In the resting state, [Ca2+]i in the nucleus and cuticular plate was variable in both types of cells. The 150 mM KCl stimulation, which might induce a depolarization, resulted in a temporary increase in [Ca2+]i in both types of cells. In the presence of 1 micron ionomycin, there was an irreversible increase in [Ca2+]i in both types of cells. These observations aid in elucidating vestibular function.

Animals↗

A new series of antiallergic agents. I. Synthesis and activity of 11-(2-aminoethyl)thio-6,11-dihydrodibenz[b,e]oxepin derivatives.

A new series of 11-substituted 6,11-dihydrodibenz[b,e]oxepin derivatives was synthesized and evaluated for antiallergic activity. Convenient methods for the preparation of sulfides from alcohols were developed. Structure-activity relationships are described. Compound 7, 11-[2-(dimethylamin)ethyl]thio-6,11-dihydrodibenz[b,e] oxepin-2-carboxylic acid hydrochloride, was the most potent in the rat passive cutaneous anaphylaxis test (ED50 = 0.92 mg/kg p.o.). It had a potent inhibitory effect on anaphylactic bronchoconstriction in guinea pigs (ED50 = 0.029 mg/kg p.o.) and H1 receptor antagonistic effect (Ki = 14 nM) with few central nervous system side effects. Additionally, an antagonistic effect against prostaglandin D2-induced contraction of isolated guinea pig trachea (pA2 = 5.73) was an attractive mechanism of action of the new antiallergic agent. Compound 7 was selected for further evaluation as KW-4994.

Animals↗

A new series of antiallergic agents. II. Synthesis and activity of new 6,11-dihydrodibenz[b,e]oxepin-carboxylic acid derivatives.

New methods for the preparation of multi-functionalized-6,11-dihydrodibenz[b,e]oxepins were developed. The structural requirements of KW-4994 (1), a promising orally active antiallergic agent, were defined. A carboxyl group at C-2 was critical for enhanced antiallergic activity of 1. The introduction of bromine atom at C-9 of 1 could elongate the duration of the action of the parent. Antiplatelet activity, a new pharmacological property of this series of compounds, was observed in one of the derivatives of 1.

Animals↗

Isolation of and calcium kinetics in cochlear inner hair cells of the guinea pig.

Single inner hair cells of the guinea pig cochlea were isolated using enzymatic and mechanical techniques. The intracellular free calcium ion concentrations [( Ca2+]i) of the isolated inner hair cells were determined using the Ca2+ sensitive dye fura-2 and digital imaging microscopy. In the presence of 1 micron ionomycin, a Ca2+ ionophore, there was an irreversible increase in [Ca2+]i. The 150 mM KCl stimulation, which induces a depolarization, resulted in a temporary increase in [Ca2+]i. This increase in [Ca2+]i was not observed under conditions of depolarization, in Ca(2+)-free medium. These observations are interpreted to mean that the [Ca2+]i during membrane depolarization mainly originates from an influx of extracellular Ca2+ into the cytoplasm.

Animals↗

[The effect of prostaglandin E1 (PGE1) on body temperature and on postoperative shivering under high dose epidural fentanyl].

Ninety-nine elective abdominal surgeries were performed under high dose epidural fentanyl anesthesia. PGE1 (0.02 microgram.kg-1.min-1 = 0.02 gamma) was administered to 34 patients (0.02 gamma group), and PGE1 (0.05 gamma) was administered to 16 patients (0.05 gamma group). PGE1 was not administered to 49 patients (control group). The effect of PGE1 on body temperature and on postoperative shivering was compared within three groups. In the 0.02 gamma group, the temperature of the fingertip was significantly higher and the rectum-fingertip temperature gradient was significantly lower than in the other groups. The forearm-fingertip temperature gradient was lower in the 0.02 gamma and 0.05 gamma groups than in the control group. The incidence of postanesthetic shivering was significantly lower in the 0.05 gamma group than in the other groups. These results suggest that; 1) PGE1 (0.02 gamma and 0.05 gamma groups) affects the peripheral blood flow and peripheral temperature, and 2) PGE1 (0.05 gamma group) significantly affects the incidence of postanesthetic shivering.

Abdomen↗

[Epidural anesthesia with high dose fentanyl for thoracic surgeries].

Twenty-two elective thoracic surgeries were performed under epidural high dose fentanyl anesthesia. These included 11 mastectomies, 3 lung lobectomies, and 8 operations for esophageal carcinoma. Through an epidural catheter, 10 micrograms.kg-1 fentanyl with [E (+)] or without [E (-)] epinephrine (1: 100,000) was given. N2O (66%) and enflurane (0.2-0.8%) were also administered, and muscle relaxants were given as needed. The onset and duration of the action were approximately 20 minutes and 3 hours, respectively. Anesthesia was maintained with enflurane (up to 0.4%) in 17 patients (77.3%). There were no differences between the E (+) group and the E (-) group. Systolic pressure, diastolic pressure and heart rate during operations were about 30% lower than those observed before the operations. Patients recovered from anesthesia rapidly. Naloxone was administered intravenously in 6 patients after mastectomies or lung lobectomies (42.9%), whose respiratory rate was below 10.min-1. The patients with short operating time (shorter than 2 hours) needed more naloxone. Troubles did not occur either in the recovery room or in the ward with both naloxone and non-naloxone groups.

Adult↗