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Biomedical subjects

H Honjo

Publications and source records attributed to H Honjo.

At least 127 records · Page 7Linked to original sources
PubMed1989

Fluctuations of membrane potential in isolated single ventricular myocytes of guinea-pig upon resumption of oxidative phosphorylation.

Electrical and mechanical activities of guinea-pig single ventricular myocytes were investigated under conditions simulating hypoxia-reoxygenation. The localized movement of sarcomere was recorded simultaneously with membrane potential, and analyzed using microcomputer-based image processing. Exposure to 5 mM CN- caused progressive shortening of action potential duration and attenuation of twitch contraction. The myocytes became inexcitable about 30 to 70 min after the CN- treatment. On removal of CN-, the myocytes exhibited periodic miniature membrane depolarizations from the resting potential level (-95 mV). When depolarizations were smaller than 6 mV in amplitude and longer than 500 ms in duration, they were accompanied by localized sarcomere shortening like a propagating contractile wave (unifocal oscillation). Membrane depolarizations of larger amplitude and shorter duration were associated with a more uniform pattern of localized sarcomere shortening (multifocal oscillation). Trains of electrical stimuli applied during the washing out period caused transient augmentation of potential fluctuation and enhancement of synchronization of sarcomere shortening. These results suggest that non-uniform elevation of intracellular calcium concentration on the resumption of oxidative phosphorylation may initiate oscillatory fluctuations of membrane potential leading to abnormal spontaneous excitation.

Action Potentials↗
PubMed1989

In vivo effects by estrone sulfate on the central nervous system-senile dementia (Alzheimer's type).

Seven women with senile dementia-Alzheimer's type (SDAT) were treated with conjugated estrogen [main content: estrone sulfate (E1-S)], at a dose of 1.25 mg/day over a 6-week period. A New Screening Test for Dementia developed by Japanese National Institute of Mental Health (NS) and the scores of Hasegawa Scale for dementia (HS) were performed every 3 weeks. Six women showed improvements in NS (P less than 0.05) and 5 women showed improvements in HS. Untreated women with SDAT did not show any improvement. Serum E1-S was measured by a direct radioimmunoassay. Serum E1-S was 911 +/- 156 pg/ml in 7 women with SDAT and lower than that of 7 normal women (1020 +/- 216 pg/ml). Following the treatment, serum E1-S increased to a level of 21.1 +/- 8.1 ng/ml. Estrone and estradiol-17 beta also increased. The results suggest a possibility for the future clinical use of estrogen for senile dementia, after careful clinical research trials including the side effects.

Aged↗
PubMed1989

Estrone sulfate and sulfatase activity in human breast cancer and endometrial cancer.

Estrone sulfate (E1-S) in the serum and tissues of patients with breast cancer or endometrial cancer was measured by a direct radioimmunoassay without hydrolysis. The concentration of E1-S in breast cancer tissue was 1.64 +/- 0.28 ng/g wet wt (+/- SE), lower than in surrounding normal breast tissue (4.46 +/- 1.23). Estradiol-17 beta(E2)/E1-S was higher in endometrial cancer tissue than normal endometrial tissue. Estrone sulfatase activity in breast cancer tissue was 0.81 +/- 0.23 nmol/h/mg protein, higher than in surrounding normal breast tissue (0.35 +/- 0.11). These results suggest that E1-S, which is abundant in the peripheral circulation, is hydrolyzed by sulfatase in breast cancer tissue or endometrial cancer tissue and liberates free estrogens, which may stimulate the growth of these malignant tumors.

Adipose Tissue↗
PubMed1989

Estrone sulfatase activity in normal and neoplastic endometrial tissues of human uterus.

Estrone sulfatase activity was measured in normal and neoplastic endometrial tissues of human uterus. The tissue homogenates were incubated in air with [3H] estrone sulfate (E1-S, 20 microM) at 37 degrees C for 30 min. After the enzyme reaction was terminated with ethyl ether, the ethyl ether extract was purified by thin-layer chromatography. The apparent Km of sulfatase was 3.0 microM, and the maximum velocity was 14.7 nmol/h/mg protein. Estrone sulfatase activity in endometrial tissues was detected throughout the menstrual cycle with no significant change. Moreover, estrone sulfatase activity in endometrial cells was not stimulated by the addition of progestogen. The enzyme activity in cancer tissue was significantly higher than in normal tissue. Thus we concluded that this enzyme may play a role in regulating the estrogen action by sifting the intracellular equilibrium between free estrogens and estrogen sulfates. We also concluded that in the endometrial cancer tissue, sulfatase appears to act on local production of estrone.

Endometrium↗
PubMed1989

Effects of propafenone on electrical and mechanical activities of single ventricular myocytes isolated from guinea-pig hearts.

1. The effects of propafenone on the transmembrane action potential and sarcomere shortening during twitch contraction were investigated in single ventricular myocytes isolated from guinea-pig hearts. 2. Propafenone at low concentrations (3-5 x 10(-7) M) slightly lengthened action potential duration (APD), but shortened it at higher concentrations. The shortening of APD was accompanied by an attenuation of sarcomere shortening during twitch contraction. 3. Propafenone (greater than 10(-6) M) caused a concentration-dependent decrease in the maximum upstroke velocity (Vmax) of the action potential. In the presence of propafenone (3 x 10(-6) M), trains of stimuli led to an exponential decline in Vmax. A time constant for the recovery of Vmax from the use-dependent block was 4.8 s. 4. In myocytes treated with propafenone (3 x 10(-6) M), the Vmax of test action potentials preceded by the conditioning clamp pulses to 0 mV was progressively decreased by increasing the duration of single clamp pulse or by increasing the number of multiple brief clamp pulses. 5. These findings suggest that propafenone has use-dependent inhibitory action on the sodium channel by binding to the channel during both activated and inactivated states, and that the unbinding rate is comparable to that of Class-I antiarrhythmic drugs with intermediate kinetics. Propafenone may also have an inhibitory action on calcium and potassium channels.

Action Potentials↗
PubMed1989

Electrophysiological effects of OPC-88117, a new antiarrhythmic agent on papillary muscles and single ventricular myocytes isolated from guinea-pig hearts.

1. The effects of OPC-88117, a new antiarrhythmic agent, on transmembrane action potentials were examined in right ventricular papillary muscles and in single ventricular myocytes isolated from guinea-pig hearts. 2. In papillary muscles, OPC-88117 above 3 x 10(-6) M caused a dose-dependent prolongation of action potential duration (APD). 3. OPC-88117 above 3 x 10(-5) M caused a significant decrease in the maximum upstroke velocity (Vmax) of the action potential without affecting the resting membrane potential. The inhibition of Vmax was enhanced at higher stimulation frequencies. 4. In the presence of OPC-88117, trains of stimuli at rates greater than or equal to 1.0 Hz led to a use-dependent inhibition of Vmax with rapid onset. The time constant for the recovery of Vmax from the use-dependent block was 456 ms. 5. The curves relating membrane potential and Vmax were shifted by OPC-88117 to the direction of more negative potentials (9 mV at 10(-4) M). 6. In single ventricular myocytes treated with OPC-88117 (1-3 x 10(-4) M), the Vmax of test action potentials preceded by conditioning clamp pulses to 0 mV was decreased progressively as the clamp pulse duration was prolonged. 7. These findings suggest that the primary electrophysiological effect of OPC-88117 on the cardiac muscle cell is prolongation of APD (Class III action) and that at high concentrations, it may also possess a lignocaine-like sodium channel inhibitory effect (Class I action).

Action Potentials↗
PubMed1989

Estrogen biosynthesis in human uterine adenomyosis.

Estrogen biosynthesis (aromatase activity) was investigated in human adenomyosis tissue and compared with that of the normal myometrium, endometrium, and endometrial cancer tissues. Homogenates were incubated with [1,2,6,7-3H]androstenedione and NADPH at 37 degrees C for 1 h. After stopping the enzymatic reaction with ethyl acetate, [4-14C]estrone and [4-14C]estradiol-17 beta were added to the incubated sample. Estrone and estradiol were purified and identified by Bio-Rad AG1-X2 column chromatography, thin-layer chromatography and co-crystallization. Estrogen formed in the incubated sample was calculated from the 3H/14C ratio of the final crystal. The value for estrone formed from androstenedione was 52-132 fmol.h-1.g-1 wet weight. Aromatase activity in the adenomyosis tissues was higher than that in normal endometrial or myometrial tissues, but lower than that found in myometrial or endometrial tumour tissue. Furthermore, we investigated the effect of danazol, progesterone, and medroxyprogesterone acetate on adenomyosis cells in primary cultures. Aromatase activity in adenomyosis was blocked by danazol, but stimulated by progesterone and MPA. These results indicate that aromatase activity in adenomyosis may contribute to the growth of the ectopic endometrial tissue which occurs in this disease.

Adult↗
PubMed1989

[Tissue culture and estrogen, to clarify the roles of estrone sulfate].

Estrone sulfate (E1-S) has been shown to be quantitatively the most important estrogen in peripheral blood. But, the physiological and/or pathological role of E1-S is not yet clarified. At present, we tried to clarify it using tissue cultures. In tissue cultures of human endometrium, secretory endometrium showed higher activity of estrone sulfatase (E1----E1-S) than proliferative endometrium. Progesterone added in the medium induced an increase of estrone sulfotransferase in the proliferative endometrium. The results suggest a reducing effect of estrogen by progesterone in secretory endometrium in physiological conditions. Estrogen dependent malignant tumors (breast cancer, endometrial cancer) have high estrone sulfatase. It converts E1-S to E1 (----E2) which are abundant in these tumors. Ishikawa cell line increased estrone sulfotransferase activity with progesterone, somewhat like the physiological conditions. From out study in vivo, there is a possibility of some ameliorative effects of E1-S on the central nervous system of patients with senile dementia (Alzheimer's type). Effects of E1-S on central nerves were investigated using tissue cultures.

Alzheimer Disease↗
PubMed1988

[Menstrual abnormality in patients with breast cancer receiving adjuvant endocrine-chemotherapy].

Menstrual status and ovarian function were studied in 24 premenopausal breast cancer patients receiving adjuvant therapy with chemotherapy and tamoxifen or chemotherapy alone. In 13 of 24 patients (54.1%), abnormal menses, including amenorrhea in 12 cases and oligomenorrhea in 1 case, developed during adjuvant therapy. In patients with abnormal menses, serum estradiol was significantly lower, and the levels of gonadotropins were significantly higher than in patients with normal menses. Among 13 patients with abnormal menses, 4 patients treated with cyclophosphamide revealed persistent amenorrhea during the whole period with adjuvant therapy, and the levels of serum estradiol and progesterone were extremely low. Furthermore, in these patients normal menses has not recovered and the levels of serum estradiol and progesterone remained low 4 to 5 months after cessation of cyclophosphamide administration. Thus, adjuvant chemotherapy caused depression of ovarian function, and cyclophosphamide induced ovarian failure, resulting in complete amenorrhea.

Adult↗
PubMed1987

Bilaminar structure of the developing stapedial footplate in the mouse--a histological study using a light microscope.

Normal development of the stapes, especially the bilaminar structure of the footplate, in the mouse was investigated histologically. On day 14 of pregnancy, the footplate had an easily distinguishable lamina consisting of two layers. This bilaminar structure was seen clearly as a pale and loose portion composed of mesenchymal cells in the vestibular side adjacent to the original footplate in the stapedial ring. The authors considered this structure to be the same structure as the lamina stapedialis in the developing human stapes. A dualistic theory of the developmental origin of the footplate in the mouse is proposed.

Animals↗
PubMed1987

Serum and urinary estrone sulfate during the menstrual cycle, measured by a direct radioimmunoassay, and fate of exogenously injected estrone sulfate.

Serum and early-morning urinary levels of estrone sulfate during the menstrual cycle were measured by a direct radioimmunoassay without hydrolysis. These levels were high and showed prominent peaks [serum, 2.67 +/- 0.37 ng/ml (mean +/- SE); urine, 5.82 +/- 2.3 micrograms/l] around the day of the preovulatory estradiol-17 beta peak, and increased again during the luteal phase. Following intravenous injection of estrone sulfate, serum estrone sulfate, estrone and estradiol-17 beta were measured. The conversion of estrone sulfate to estrone and/or estradiol-17 beta was very small during their transit in the general circulation.

Adolescent↗
PubMed1987

Endocardial excitation and conduction during reperfusion arrhythmias.

In order to clarify the role of Purkinje fibers in the occurrence of reperfusion arrhythmias, endocardial mapping was performed on perfused canine hearts by attaching 42 close bipolar electrodes to the endocardial surface of the left ventricular septum. Reperfusion with oxygenated Krebs-Ringer solution following 30 min of coronary occulusion induced ventricular tachycardia (VT) in 14 out of 23 preparations. These VT degenerated into ventricular fibrillation (VF) within 1 min after the reperfusion in all but 3 cases. Endocardial mapping revealed that the excitations during VT were always initiated by the Purkinje activities and that myocardial excitations were expanded in a centrifugal manner through Purkinje-muscle junctional area. Furthermore, this excitation pattern was preserved, in the early phase of VT, even though the propagation pattern was distorted. VF was always induced by reperfusion following 30 min of ischemic condition, that is, coronary perfusion with a hyperkalemic (K = 10 mM), acidic (pH = 6.8) and hypoxic (PO2 = 20-40 mmHg) solution (4/4 cases). Elimination of hyperkalemia from the ischemic condition markedly prevented occurrence of VF (1/6 cases) during reperfusion but it did not affect occurrence of VT (4/6 cases); this implies that hyperkalemia causes the onset of VF but has less effect on the occurrence of VT. It has been separately confirmed by micro-electrode experiment, using the dissected papillary muscle of the canine right ventricle, that abnormal impulse formation during re-oxygenation was triggered in Purkinje fibers around Purkinje-muscle junction.

Animals↗