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Biomedical subjects

H Honjo

Publications and source records attributed to H Honjo.

At least 91 records · Page 5Linked to original sources
PubMed1996

Effect of estrogen replacement therapy on hepatic triglyceride lipase, lipoprotein lipase and lipids including apolipoprotein E in climacteric and elderly women.

Estrogen provides beneficial effects on hyperlipidemia in climacteric and elderly women. In this study of 68 women (37 to 67 years old), hepatic triglyceride lipase (HTGL), lipoprotein lipase (LpL) serum lipids and apolipoproteins were analyzed to investigate the effects of estrogen replacement therapy (ERT). After menopause, LpL, total cholesterol, low-density lipoprotein (LDL)-cholesterol, and apolipoprotein B increased. But ERT suppressed total cholesterol, LDL-cholesterol, apolipoprotein B, and especially apolipoprotein E in menopausal women. The mechanism was thought that ERT significantly suppressed HTGL, but LpL was not affected. Estrogen also increases hepatic LDL receptors and accelerates transfer of serum LDL-C (and TC). It was said that HTGL accelerates conversion of intermediate-density lipoprotein (IDL) to LDL. The suppression of HTGL by the ERT may decrease conversion of IDL to LDL and lower LDL-C (and TC). These estrogen's beneficial effects on lipids, may prevent the atherosclerosis. In addition, apolipoprotein E increases senile plaques in senile dementia-Alzheimer's type. The decrease in apolipoprotein E with ERT may be related to cognitive functions of elderly women.

Adult↗
PubMed1996

Acute and chronic effects of amiodarone on mammalian ventricular cells.

This article reviews experimental studies on the electrophysiological effects of amiodarone on mammalian hearts. Acute application of amiodarone (0.1-10 microM) to papillary muscles or single ventricular cells isolated from rabbits or guinea pigs caused a significant decrease in action potential duration (APD) as well as a marked use-dependent inhibition of the maximum upstroke velocity (Vmax) of action potential with fast recovery kinetics. Acute amiodarone also caused a concentration-dependent decrease in the calcium current (ICa) and the delayed-rectifier potassium current (IK). Action potentials recorded from papillary muscles or single ventricular cells isolated from the rabbits treated with oral amiodarone (100 mg/kg daily, 4 weeks) were characterized by a moderate frequency-independent prolongation of APD. There was no use-dependent Vmax inhibition. The ventricular cells treated with chronic amiodarone showed a significant decrease in the current density of ICa, IK and Ito. The amount of mRNA for Kv1.5, a Shaker-related potassium channel from the rats treated with chronic oral amiodarone was significantly lower than that from control rats. These results suggest that the major and consistent effects of chronic amiodarone is repolarization delay (Class III action) through a decrease in IK and Ito density, probably due to a modulation of gene expression of potassium channels. When amiodarone above a certain concentration is present in the extracellular space, fast kinetic Class I and Class IV actions would be added as acute effects.

Action Potentials↗
PubMed1996

[Effects of gonadotropin-releasing hormone and its analogue (buserelin) on aromatase in cultured human granulosa cells].

We studied the direct effects of gonadotropin-releasing hormone (GnRH) and its analogue (buserelin) on aromatase activity and the aromatase cytochrome P-450 (P-450arom) concentration in cultured human granulosa cells which were obtained during oocyte retrieval for in vitro fertilization. Aromatase activity was assessed by radioassay with [1beta-3H]androstenedione as the substrate. The P-450arom concentration was determined by an enzyme-linked immunosorbent assay with specific antibodies to P-450arom. Buserelin stimulated aromatase activity and P-450arom at low concentrations (10(-13) - 10(-9)M), but it suppressed these parameters at high concentrations (10(-8) - 10(-7)M). The stimulatory effect increased with time during 12- to 48-h culture and disappeared after 72-h culture. Follicle-stimulating hormone (FSH) (100 ng/ml) stimulated aromatase activity and the P-450arom concentration but, FSH stimulation was suppressed by co-administration of low or high concentrations of buserelin. In contrast GnRH suppressed aromatase activity and P-450arom at all concentrations (10(-12) - 10(-6)M). GnRH also suppressed FSH stimulation of aromatase. Aromatase activity was correlated with the P-450arom concentration. These results suggest that in human preovulatory granulosa cells, buserelin and GnRH modulate aromatase activity by changing the P-450arom concentration.

Aromatase↗
PubMed1996

[Autonomic regulation of pacemaker activity in the sinoatrial node].

Recent technical advances have made it possible to investigate quantitatively the ionic events underlying pacemaker activity in the sinoatrial node. Various time-dependent currents through ion channels such as the delayed rectifier K current, two types of Ca currents and the hyperpolarization-activated current have been found to play an important role in the generation of the pacemaker activity of sinoatrial node cells. Time-independent background currents, transporter-mediated current and pump current also contribute to pacemaker activity. In this article, the physiological significance of these currents for the pacemaker depolarization and their modulation by autonomic nerves and humoral factors are discussed.

Autonomic Nervous System↗
PubMed1995

Computer simulation of the electrotonic modulation of pacemaker activity in the sinoatrial node by atrial muscle.

Electrotonic interaction between the sinoatrial (SA) node and surrounding atrial muscle was investigated in a computer simulation using a modified Oxsoft HEART model (Oxsoft, Oxford, UK). When an SA node cell model was coupled to a passive atrial membrane model (RC circuit) with various coupling conductances (Gc), there was a Gc-dependent prolongation of spontaneous cycle length (SCL). At a sufficiently high value of Gc, the spontaneous activity was finally stopped. A nonlinear relationship between Gc and SCL was obtained, similar to that observed in experiments on rabbit SA node cells. When the muscarinic potassium current (iK,ACh) was activated in the SA node cell model, the coupling-induced inhibition of pacemaker activity was potentiated. Although coupling current and iK,ACh were additive, their effects on SCL were more than additive because of the nonlinear dependence of SCL on net current. A decrease in the input resistance of the atrial membrane model to stimulate the activation of iK,ACh in atrial muscle was also shown to potentiate the coupling-induced inhibition of SA node spontaneous activity.

Action Potentials↗
PubMed1995

Senile dementia-Alzheimer's type and estrogen.

Some reports have suggested the ameliorative effects of estrogens on clinical symptoms, such as short memory, in women suffering from senile dementia-Alzheimer's type, in vivo. The action mechanism of estrogen remains to be clarified, but 1) an anti-depressive effect, 2) improvement of cerebral blood flow, 3) direct stimulation of neuron, 4) development of gliacyte and 5) suppression of apolipoprotein E have been suggested. Some mechanisms may be combined, contributing to the beneficial effects on clinical symptoms.

Alzheimer Disease↗
PubMed1995

Modulation of pacemaker activity of sinoatrial node cells by electrical load imposed by an atrial cell model.

To investigate the electrotonic modulation of sinoatrial (SA) node pacemaker activity by atrial muscle, single or multiple (2-7) SA node cells isolated from rabbit hearts were connected to a membrane model [resistance-capacitance (R-C) circuit] of an atrial cell through an external circuit that mimics the gap junctional conductance (Gc) between cells. When Gc was 0 nS (uncoupled conditions), all the preparations generated regular and stable spontaneous action potentials with a mean cycle length (SCL) of 263 +/- 45 ms (+/- SD, n = 35). Step increases of Gc were associated with a progressive prolongation of SCL. At sufficiently high values of Gc, the spontaneous activity became irregular and finally stopped. We defined the threshold Gc causing an appreciable SCL irregularity as the minimum Gc at which the ratio of SD to mean of SCL was > 0.3. The threshold Gc for a single SA node cell was calculated to be 0.58 nS. In the presence of acetylcholine (ACh; 0.05-0.2 microM), the coupling-induced inhibition of spontaneous activity was greatly increased, and the threshold Gc for a single SA node cell was decreased in a concentration-dependent manner. These findings show that the pacemaker activity of SA node cells is easily inhibited when the cells are coupled to a passive atrial cell model and the inhibition is amplified by ACh. Computer simulation using a modified Oxsoft HEART model indicates that the passive atrial cell model acts as a current sink, imposing a substantial outward current on the SA node cell, and ACh amplifies the effect by activating an additional outward current.

Acetylcholine↗
PubMed1995

[Effect of acupuncture on the overactive bladder].

BACKGROUND: We examined the effect of acupuncture for the overactive bladder. METHODS: Eleven patients (9 males and 2 females) with the overactive bladder were treated with acupuncture. The age of the patients ranged from 51 to 82 years (mean 71 years). Nine patients complained of urge incontinence and 2 patients of urgency. Uninhibited contraction was observed in all patients before the acupuncture. A disposable needle (0.3 mm in diameter, 60 mm in length) was inserted into bilateral BL-33 points at the depth of 50 to 60 mm and was rotated for 10 minutes manually. The treatment was performed 4 to 12 (average 7 times). RESULTS: Urge incontinence was controlled completely in 5 and partially in 2 of 9 patients. In 2 patients who complained urgency complete response was obtained after the treatment. Uninhibited contraction disappeared in 6 patients after the treatment. Acupuncture induced an increase of maximum bladder capacity and bladder compliance with statistical significance (p < 0.01 and p < 0.05), respectively. CONCLUSION: Acupuncture at the BL-33 point was effective for controlling the overactive bladder.

Acupuncture Therapy↗
PubMed1995

Ionic basis of the chronotropic effect of acetylcholine on the rabbit sinoatrial node.

OBJECTIVE: The aim was to study the ionic basis of the chronotropic effects of bath applied acetylcholine and vagal stimulation on the rabbit sinoatrial node. METHODS: The chronotropic effect of bath applied acetylcholine was measured in single cells and small multicellular preparations from the rabbit sinoatrial node and the chronotropic effect of postganglionic vagal stimulation was measured in the intact sinoatrial node. The roles of the hyperpolarisation activated current, i(f), the acetylcholine activated potassium current, iK,ACh, and the L-type calcium current, iCa, were investigated by blocking the currents with 1-2 mM Cs+ or 10(-6) M UL-FS49, 0.2-1.0 mM Ba2+, and 6 x 10(-6) M nifedipine, respectively. RESULTS: Under control conditions, small multicellular preparations were approximately two orders of magnitude less sensitive to bath applied acetylcholine than single cells. However, after block of acetylcholinesterase by eserine in small multicellular preparations the sensitivities of the two types of preparation were approximately the same. Block of i(f) either had no discernible effect or increased the chronotropic effect of bath applied acetylcholine on single cells or small multicellular preparations, whereas partial block of iK,ACh reduced it substantially. Similarly, block of i(f) did not suppress the initial slowing of spontaneous action potentials by vagal stimulation, whereas partial block of iK,ACh reduced it. The hyperpolarisation of the arrested sinoatrial node in response to vagal stimulation was also substantially reduced by block of iK,ACh. Partial block of iCa caused large decreases in the action potential amplitude and maximum diastolic potential, but little decrease in the rate of spontaneous action potentials, and therefore did not mimic the effect of acetylcholine. CONCLUSIONS: The chronotropic effects of bath applied acetylcholine and vagal stimulation are not principally the result of a suppression of i(f) or iCa, whereas the activation of iK,ACh may play an important role.

Acetylcholine↗
PubMed1994

Ultra-slow voltage-dependent inactivation of the calcium current in guinea-pig and ferret ventricular myocytes.

L-type Ca2+ current, iCa, has been recorded in guinea-pig ventricular myocytes at 36 degrees C using the whole cell patch clamp technique. Intracellular Ca2+ was buffered with ethylenebis(oxonitrilo)tetraacetate (EGTA). An increase in the rate of stimulation from 0.5 to 3 Hz resulted in an abrupt decrease in iCa in the first beat at the high rate, followed by a progressive decrease (tau approx. 7 s) over the next 30 s. The changes were not the result of Ca(2+)-dependent inactivation, because similar changes occurred with either Ba2+ or Na+ as the charge carrier. During 20-s voltage clamp pulses there was an ultra-slow phase of inactivation of Ba2+ or Na+ current through the Ca2+ channel (tau approx. 6 s at 0 mV). This was confirmed by applying test pulses after conditioning pulses of different duration: the Ba2+ current during the test pulse decreased progressively when the duration of the conditioning pulse was increased progressively to 20 s. Ultra-slow inactivation of Ba2+ current was voltage dependent and increased monotonically at more positive potentials. Recovery of Ba2+ current from ultra-slow inactivation occurred with a time constant of 3.7 s at -40 mV and 0.7 s at -80 mV. The gradual decrease in iCa on increasing the rate to 3 Hz may have been the result of the development of ultra-slow voltage-dependent inactivation.

Animals↗
PubMed1993

[The histochemical study of the effects of estrogen on the forebrain cholinergic neurons of fetal female rats transplanted into the anterior eye chamber of adult female rats].

In order to clarify the effects of estrogen on cholinergic basal forebrain neurons, a cholinergic neuron in the diagonal band nucleus of the female fetal rat was implanted into the anterior eye chamber of the female adult rat. Some host rats were treated with 2mg estradiol valerate (E2v) injected every 3 days after ovariectomy while others were not 2 and 4 weeks after transplantation, the growth of cholinergic neurons in the graft was studied using acethylcholinesterase (AChE) histochemistry. At 2 weeks after transplantation, AChE positive neurons and fibers were densely distributed in the grafts of E2v treated rats. Also in grafts without E2v treatment, AChE positive neurons and fibers were found in all the grafts although their density was low. At 4 weeks, AChE staining was dense staining observed in both groups. These results indicate that neurotrophic effect of estrogen on the cholinergic basal forebrain neurons.

Acetylcholinesterase↗
PubMed1993

Cigarette smoking during pregnancy lowers aromatase cytochrome P-450 in the human placenta.

To clarify whether cigarette smoking during pregnancy causes an organic alteration in placental estrogen producing ability, we determined the catalytic activity of aromatase by the tritiated water assay, and tissue level of aromatase cytochrome P-450 (P-450arom) by the specific enzyme-linked immunosorbent assay, in placental samples from nonsmokers and smokers. As pregnancy progressed, both aromatase activity and P-450arom concentration increased in placentas from nonsmokers and smokers. However, the gradient of the increase was significantly less in heavy smokers (> or = 20 cigarettes a day) than in normal and moderate smokers (< 20 cigarettes a day). At term, the mean aromatase activity and P-450arom concentration in placentas from heavy smokers were significantly lower than in nonsmokers and moderate smokers, while aromatase activity per P-450arom (turnover rate) and the mean placental weight were comparable among the three groups. In contrast, the ratio of aryl hydrocarbon hydroxylase activity to aromatase activity was higher in placentas from heavy smokers. Immunohistochemical studies showed that P-450arom was localized in the cytoplasm of syncytiotrophoblasts of chorionic villi in placentas from both nonsmokers and smokers. These results suggest that the induction of placental P-450arom during gestation is suppressed by maternal smoking, resulting in a reduction in estrogen producing ability, while placental xenobiotic P-450 is induced.

Aromatase↗
PubMed1993

Estrogen productivity of endometrium and endometrial cancer tissue; influence of aromatase on proliferation of endometrial cancer cells.

Aromatase, estrone (E1) sulfatase and E1 sulfotransferase activities were examined in endometrium and endometrial cancer tissue preparations. Aromatase and E1 sulfatase activities in endometrial cancer tissues were found to be significantly higher than in normal endometrial tissues. However, E1 sulfotransferase activity did not differ between benign and malignant tissue. We also examined the effect of testosterone (T) on aromatase activity and tritiated thymidine uptake (DNA synthesis) in various cultured cervical or corpus endometrial cancer cell lines (OMC-4, HHUA, Ishikawa, HEC-59). The results demonstrated that only the HEC-59 cell line had high aromatase activity and increased its DNA synthesis in response to T. This increase of DNA synthesis by T was not suppressed by simultaneous addition of cyproterone acetate, but was by tamoxifen. These data suggest that in situ estrogen production in endometrial cancer tissue is biologically important and that aromatase in cancer cells may contribute partially to cell proliferation if androgen substrate is provided.

Aromatase↗
PubMed1993

On the role of G protein activation and phosphorylation in desensitization to acetylcholine in guinea-pig atrial cells.

1. The ACh-activated K+ current (IK,ACh) has been investigated in guinea-pig atrial cells at 36 degrees C using the whole-cell patch-clamp technique. 2. During an exposure to ACh, IK,ACh faded as a result of desensitization. Throughout the fade of the current, the current reversed at EK and showed inward-going rectification. The fade was, therefore, the result of a genuine decrease in IK,ACh. 3. The onset of desensitization (as judged by the fade of IK,ACh) was biphasic and the time constants of the fast and slow phases of desensitization were 1.58 +/- 0.14 (n = 16) and 148.2 +/- 12.8 s (n = 18) respectively. Recovery from the fast and slow phases of desensitization (after 30 s and 5 min exposures to ACh respectively) occurred with time constants of 52 and 222 s respectively. This suggests that two processes are involved in desensitization. 4. The Q10 of the rate constant of the fast phase of desensitization was 2.2 +/- 0.3 (n = 6). 5. Intracellular perfusion with guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) or extracellular perfusion with AlF4- were used to bypass the muscarinic receptor and trigger IK,ACh by directly activating the G protein, GK, that links the muscarinic receptor to the K+ channel. Both GTP gamma S and AlF4- activated a current with the same reversal potential and the same degree of inward-going rectification as the ACh-activated current. 6. Desensitization still occurred when the muscarinic receptor was bypassed and IK,ACh was triggered by direct activation of GK with either GTP gamma S or AlF4-. This suggests that desensitization is, in part, the result of a modification of either GK or the K+ channel. 7. Activation of the muscarinic receptor by ACh resulted in greater desensitization than direct activation of GK; at the end of a 5 min exposure to ACh, current was only 22 +/- 1% (n = 19) of its peak value, whereas, after direct activation of GK by GTP gamma S for 5 min, current was 42 +/- 6% (n = 5) of its peak value. This suggests that desensitization also involves the muscarinic receptor. 8. When cells were perfused with GTP gamma S, the fast phase of desensitization could still occur, but the slow phase was reduced. This suggests that the fast phase involves GK or the K+ channel, whereas the slow phase involves the muscarinic receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1992

[Endogenous levels and dynamics of estrogen sulfates--physiological and pathological roles of estrone sulfate and estradiol 17-sulfate].

Plasma ethinylestradiol increases 47.6% when taken with ascorbic acid because of competition in producing sulfate conjugation. Thus the role of sulfates may be important. Serum and urinary estrone sulfate (E1-S) in pregnancy and non-pregnancy were analyzed. Its serum peak during the menstrual cycle was 2.67 +/- 0.37 ng/ml (mean +/- SE) and about ten times that of estradiol-17 beta. E1-S showed lower levels in malignant tissues of breast cancer and endometrial cancer. Increased sulfatase activity in the malignant tissue hydrolyzes E1-S to E1, which may develop the tumors. Serum estradiol 17-sulfate (E2-17-S) in pregnancy was first measured. As E2-17-S decreased, lipid peroxides increased. E2-17-S is converted to 2-OH or 4-OH E2-17-S, which act as lipid peroxide scavengers. Pregnancy-induced hypertension showed lower levels of E2-17-S. In vitro study using the human endothelial cell of the aorta, E2-17-S and 2-OH E2-17-S strongly suppressed lipid peroxidation, which precedes atherosclerotic change.

Adult↗