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Biomedical subjects

Y Sakuma

Publications and source records attributed to Y Sakuma.

At least 73 records · Page 4Linked to original sources
PubMed1998

Effects of an ACE inhibitor and a calcium channel blocker on cardiovascular autonomic nervous system and carotid distensibility in patients with mild to moderate hypertension.

We investigated the relationship between cardiovascular autonomic nervous system function and carotid arterial distensibility during treatment with an angiotensin converting enzyme inhibitor (derapril) or a calcium channel blocker (manidipine) for hypertension. In 37 patients with hypertension, autonomic function was assessed by heart rate variability and baroreceptor sensitivity using phenylephrine injection. Left ventricular mass index and carotid arterial distensibility were assessed by ultrasound examinations. Before the medication, both baroreceptor sensitivity and heart rate variability correlated with carotid arterial distensibility, but not with left ventricular mass index by multiple regression analysis. Subsequently, patients were randomly allocated into two groups, derapril (n = 18) and manidipine (n = 19) for 20 weeks. At the end of the study, the change in baroreceptor sensitivity correlated with change in carotid arterial distensibility (r = 0.41, P < .05), but not with change in left ventricular mass index. Although derapril and manidipine decreased blood pressure and left ventricular mass index to the same extent, the former improved heart rate variability, baroreceptor sensitivity (5.0 +/- 1.9 --> 5.6 +/- 2.0 msec/mm Hg), and carotid arterial distensibility (2.1 +/- 0.8 --> 2.5 +/- 1.0 %kPa), but the latter did not improve them at all. Thus, impairment of the autonomic balance was related to the impairment of carotid arterial distensibility in hypertension; derapril, but not manidipine, significantly improved these abnormalities.

Aged↗
PubMed1998

Inhibitors of acyl-CoA:cholesterol O-acyltransferase (ACAT). Part 1: identification and structure-activity relationships of a novel series of substituted N-alkyl-N-biphenylylmethyl-N'-arylureas.

A series of N-alkyl-N-biphenylylmethyl-N'-arylurea and related derivatives represented by 1 have been prepared and evaluated for their ability to inhibit acyl-CoA:cholesterol O-acyltransferase in vitro and to lower plasma cholesterol levels in cholesterol-fed rats in vivo. Linking of two phenyl groups via oxygen and introduction of fluorine at appropriate positions on the biphenyl moiety improved in vitro and in vivo activity. From this series of analogs, compound 40 (FR179254), which had potent in vitro potency (rabbit intestinal microsomes IC50 = 25 nM), showed excellent plasma cholesterol-lowering activity when administered via the diet (ED50 = 0.045 mg/kg). However, the hypocholesterolemic effect of this compound was moderate when dosed by oral gavage in PEG400 as a vehicle (ED50 = 5.3 mg/kg). Modification of the N'-aryl moiety led to the identification of compound 50 (FR182980) which was efficacious in both dosing models (ED50 = 0.034 mg/kg and 0.11 mg/kg, respectively).

Anilides↗
PubMed1998

Two transcription factors, DREB1 and DREB2, with an EREBP/AP2 DNA binding domain separate two cellular signal transduction pathways in drought- and low-temperature-responsive gene expression, respectively, in Arabidopsis.

Plant growth is greatly affected by drought and low temperature. Expression of a number of genes is induced by both drought and low temperature, although these stresses are quite different. Previous experiments have established that a cis-acting element named DRE (for dehydration-responsive element) plays an important role in both dehydration- and low-temperature-induced gene expression in Arabidopsis. Two cDNA clones that encode DRE binding proteins, DREB1A and DREB2A, were isolated by using the yeast one-hybrid screening technique. The two cDNA libraries were prepared from dehydrated and cold-treated rosette plants, respectively. The deduced amino acid sequences of DREB1A and DREB2A showed no significant sequence similarity, except in the conserved DNA binding domains found in the EREBP and APETALA2 proteins that function in ethylene-responsive expression and floral morphogenesis, respectively. Both the DREB1A and DREB2A proteins specifically bound to the DRE sequence in vitro and activated the transcription of the b-glucuronidase reporter gene driven by the DRE sequence in Arabidopsis leaf protoplasts. Expression of the DREB1A gene and its two homologs was induced by low-temperature stress, whereas expression of the DREB2A gene and its single homolog was induced by dehydration. Overexpression of the DREB1A cDNA in transgenic Arabidopsis plants not only induced strong expression of the target genes under unstressed conditions but also caused dwarfed phenotypes in the transgenic plants. These transgenic plants also revealed freezing and dehydration tolerance. In contrast, overexpression of the DREB2A cDNA induced weak expression of the target genes under unstressed conditions and caused growth retardation of the transgenic plants. These results indicate that two independent families of DREB proteins, DREB1 and DREB2, function as trans-acting factors in two separate signal transduction pathways under low-temperature and dehydration conditions, respectively.

Adaptation, Physiological↗
PubMed1998

[DNA bend sites in the promoter region of the human estrogen receptor alpha gene].

DNA bend sites in the promoter region of the human estrogen receptor a gene were determined by the circular permutation assay. Among a total of five sites (ERB -4 to -1, and ERB + 1) mapped in the 3 kb region, three matched with the positions of the predicted periodicity while the other two did not. Most of the sites were accompanied by the short poly (dA)-poly (dT) tracts including the potential bend core sequence A2N8A2N8A2 (A/A/A). Fine mapping of the ERB-2 site indicated that this A/A/A and the immediate franking sequences contained motifs for the estrogen response element. This region had a higher affinity for the nuclear scaffold and was included in the core region of the nucleosome structure. However, binding of the nuclear factor(s) to the motifs and disruption of nucleosome structure occurred without ATP. These results suggest that a class of periodic bent DNA could act as a site of multiple interactions among the nuclear scaffold, core histones and nuclear factors.

DNA↗
PubMed1998

Temporal coincidence between the excitation of ventromedial hypothalamic efferents and the induction of lordosis reflex in ovariectomized estrogen-primed rats.

The temporal changes in excitability in ventromedial hypothalamic neurons which project to the midbrain central gray caused by chronic estrogen exposure were measured in ovariectomized rats. In 66 urethane-anesthetized animals which had either no capsule, or had a capsule containing estrogen implanted for 24 h, 48 h, 72 h or 96 h, 189 antidromic action potentials were recorded in the ventromedial hypothalamus (VMN) in response to stimulation of the midbrain central gray (CG). The antidromic activation threshold was lower in 40 recordings made from the VMN in the 72-h or 96-h group than in 67 from the no-treatment, 24-h or 48-h group. The decrease in the threshold coincided with the emergence of the lordosis reflex. In a separate cohort of ovariectomized rats, any absence of estrogen for 2-48 h before and during the measuring abolished the neuronal as well as the behavioral effects at 72 h. The results suggest that the lordosis reflex induced by estrogen alone depends on the excitation of VMN efferents to the CG. In addition, the indispensability of estrogen at the time of electrophysiological and behavioral evaluation indicates that a certain direct neural action of estrogen is involved in the behavioral activation.

Animals↗
PubMed1998

Gonadotropin-releasing hormone (GnRH) innervation of the pituitary in a cichlid fish, Oreochromis niloticus: a brain lesion study.

In most vertebrates, multiple gonadotropin-releasing hormone (GnRH) neuronal groups have been reported. In tilapia three GnRH neuronal groups (terminal nerve, preoptic, midbrain) have been reported. Which of the three GnRH cell groups regulate the pituitary is not well known. We performed brain lesions of each neuronal group and studied immunocytochemically the changes of GnRH fiber distribution in the pituitary. Lesions of the preoptic cell group resulted in almost complete absence of GnRH fibers in the neurohypophysis of the proximal pars distalis. After lesions of the terminal nerve GnRH cell group, no changes were observed in the distribution of GnRH fibers in the pituitary. Lesions of the midbrain cell group were unsuccessful because of high mortality. The present study indicates that the preoptic GnRH cell group is the main contributor of the pituitary innervation.

Animals↗
PubMed1998

[Clinical study on 17 cases of genitourinary tuberculosis].

Between 1987 and 1995, 17 patients with genitourinary tuberculosis were treated at Iwate Prefectural Central Hospital. The incidence of newly diagnosed genitourinary tuberculosis was 17 out of 16,363 outpatients (0.1%) during the 9-year period. Twelve patients had urinary tuberculosis and genital as well as urinary organs were affected in 5. Six (35%) patients presented in their fifties and 5 (29%) each in their forties and sixties. Nine (53%) patients had irritative voiding symptoms as the chief complaint. Only 29% had a known history of extra-genitourinaty tuberculosis. In addition to the standard multidrug chemotherapy, nephrectomy was performed in 5 patients and orchiectomy in 2 with epididymal tuberculosis. The incidence of tuberculosis has recently increased in many parts of our country and more attention should be paid to genitourinary tuberculosis.

Adult↗
PubMed1998

Importance of the medial amygdala in rat penile erection evoked by remote stimuli from estrous females.

Effects of medial amygdala lesions (MAL) were examined on rat penile erection in three different experimental situations. Only sexually vigorous males, as identified by preoperative mating tests, were used. Bilateral radiofrequency lesions were confined to the posterior medial amygdala, with little systematic damage to anterior medial amygdala or to adjacent structures. Lesion electrodes were withdrawn without current application in sham-operated animals (SHAM). After recovery for brain surgery, males were tested for (1) noncontact erection (NCE) that occurs when males were placed in proximity to inaccessible estrous females, (2) reflexive erection evoked in supine males by retraction of the penile sheath, and (3) copulatory behaviour with receptive females. In the NCE test, none of the MAL males showed penile erection during the 20 min observation, whereas 70% of the SHAM males showed it (P < 0.001). In contrast, no erectile dysfunction in the MAL males was detected in the other two tests. MAL males displayed more penile-body erections (flips) than SHAM males in the reflexive-erection test (P <0.05). In the copulation test, most of the MAL males achieved intromission, but their intromission ratio, a partial measure of erectile function, was marginally lower than that of SHAM males (P = 0.051). MAL males had longer intervals between intromissions (P < 0.001); as a result, none of them ejaculated during the 30 min period that followed the first intromission. The results suggest that the posterior medial amygdala plays an essential role in the regulation of NCE, and it may also contribute to the regulation of erection in other contexts.

Amygdala↗
PubMed1997

Estrogen alleviates cognitive dysfunction following transient brain ischemia in ovariectomized gerbils.

Capability of estrogen to alleviate spatial-learning deficits due to brain ischemia was evaluated in ovariectomized gerbils. Thirty-nine ovariectomized gerbils were physically trained to swim in a 90 cm-diameter round pool. The half of the ovariectomized animals received subcutaneous implantation of a Silastic capsule of estrogen, 1 week before ischemic assault. Transient brain ischemia was accomplished on experimental day 1 by bilateral clipping of the common carotid artery for 15 min under pentobarbital and ketamine anesthesia. On day 3 and onwards, daily Morris water-maze task was imposed. Although estrogen-treated non-ischemic animals spent longer time in the water, their distances swam were not different from non-treated animals: estrogen had no effect on the spatial learning to take the shortest distance to get to the submerged table. In the ovariectomized non-treated gerbils, ischemia prolonged the time in the water and lengthened the distance swam. Among the ischemic gerbils, those given estrogen swam a significantly shorter distance than the non-treated animals. The results indicate that estrogen alleviates the ischemia-induced deficits in the acquisition of the water-maze task. The results also defy previous association of estrogen with decreased acquisition of the water-maze task, which was based principally on the prolonged time in the water.

Animals↗
PubMed1997

ER-27319, an acridone-related compound, inhibits release of antigen-induced allergic mediators from mast cells by selective inhibition of fcepsilon receptor I-mediated activation of Syk.

Engagement of the mast cell high-affinity receptor for immunoglobulin E (IgE), FcepsilonRI, induces tyrosine phosphorylation of Syk, a non-receptor tyrosine kinase, that has been demonstrated as critical for degranulation. Herein we describe a synthetic compound, ER-27319, as a potent and selective inhibitor of antigen or anti-IgE-mediated degranulation of rodent and human mast cells. ER-27319 affected neither Lyn kinase activity nor the antigen-induced phosphorylation of the FcepsilonRI but did effectively inhibit the tyrosine phosphorylation of Syk and thus its activity. As a consequence, tyrosine phosphorylation of phospholipase C-gamma1, generation of inositol phosphates, release of arachidonic acid, and secretion of histamine and tumor necrosis factor alpha were also inhibited. ER-27319 did not inhibit the anti-CD3-induced tyrosine phosphorylation of phospholipase C-gamma1 in Jurkat T cells, demonstrating a specificity for Syk-induced signals. In contrast the tyrosine phosphorylation and activation of Syk, induced by in vitro incubation with the phosphorylated immunoreceptor tyrosine-based activation motif (ITAM) of FcepsilonRI gamma subunit or by antigen activation of RBL-2H3 cells, was specifically inhibited by ER-27319. However, when ER-27319 was added to immunoprecipitated Syk, derived from activated cells, no effect was seen on Syk activity. ER-27319 did not inhibit the tyrosine phosphorylation of Syk induced by activation in the presence of Igbeta ITAM or the anti-IgM-induced phosphorylation of Syk in human peripheral B cells. Therefore, ER-27319 selectively interferes with the FcepsilonRI gamma phospho-ITAM activation of Syk in vitro and in intact cells. These results confirm the importance of Syk in FcepsilonRI-mediated responses in mast cells and demonstrate the mast cell selectivity and therapeutic potential of ER-27319 in the treatment of allergic disease.

Acridines↗
PubMed1997

GnRH inhibits neuronal activity in the ventral tegmental area of the estrogen-primed ovariectomized rat.

In urethane-anesthetized ovariectomized rats, estrogen-sensitive descending neurons were identified in the midbrain ventral tegmental area (VTA), based on estrogen-induced changes in the excitability in antidromic responses to midbrain central gray stimulation. Estrogen increased the threshold and decreased the firing rate of the identified neurons. Responses of the identified neurons to the microiontophoresis of gonadotropin-releasing hormone (GnRH) or D-Phe2, D-Ala6-GnRH, a behaviorally active analog, but not to glutamate or gamma-aminobutyric acid (GABA), depended on estrogen. In the ovariectomized rat, GnRH excited a few neurons; the analog had no effect. GnRH suppressed spontaneous or glutamate-induced firing in almost all neurons in the estrogen-primed rat. The analog had mixed effects. The facilitation of female rat sexual behavior induced by infusion of GnRH in the VTA is due to the inhibition of VTA neurons.

Animals↗
PubMed1997

Estrogen-excitable forebrain projections to the ventral premammillary nucleus of the female rat.

Retrograde labels by Nuclear Yellow from the female rat ventral premammillary nucleus (PMv) were most numerous in the lateral septum (LS) and the preoptic area (POA) and spread laterally into the substantia innominata. Other labels were in the diagonal band nucleus, the substantia innominata and the bed nucleus of the stria terminalis. Constant-current, single-pulse electrical stimulation of the PMv in urethane-anesthetized ovariectomized rats elicited antidromic action potentials in the cingulate cortex, in addition to the structures that contained labeled neurons. In the LS or cingulate cortex, but not in the POA, estrogen decreased antidromic activation thresholds and shortened refractory periods. The PMv is a way station that relays estrogen-excitable septal, but not preoptic, effects. The PMv also contains fibers of passage that originate in estrogen-excitable cingulate neurons.

Animals↗
PubMed1997

Effects of FR145237, an acyl-CoA:cholesterol acyltransferase inhibitor, on diet-induced hypercholesterolemia in diabetic rats.

Recent studies have shown that acyl-CoA:cholesterol acyltransferase (ACAT) plays an important role in the initiation of diabetes-associated hypercholesterolemia. To confirm this hypothesis, effects of a potent ACAT inhibitor, FR145237, on diet-induced hypercholesterolemia were examined in streptozotocin (STZ)-induced diabetic rats. One-week feeding of 1% cholesterol and 0.5% cholic acid to normal rats and STZ-induced diabetic rats increased plasma cholesterol levels in both groups, and the response was more remarkable in the STZ rats than in the normal ones (1266 +/- 476 mg/dl and 146 +/- 7 mg/dl, respectively). FR145237 dose-dependently reduced the rise in plasma cholesterol levels in the STZ rats and the levels were almost normalized by treatment with 1 mg/kg/day of the compound. These results suggest that hyperresponse to dietary cholesterol was induced in the STZ rats and that ACAT is involved in the hyperresponse. The effects of FR145237 on other plasma lipids such as high density lipoprotein (HDL) cholesterol and triglyceride (TG) levels were also examined.

Animals↗
PubMed1997

Importance of the medial amygdala in rat penile erection evoked by remote stimuli from estrous females.

Effects of medial amygdala lesions (MAL) were examined on rat penile erection in three different experimental situations. Only sexually vigorous males, as identified by preoperative mating tests, were used. Bilateral radiofrequency lesions were confined to the posterior medial amygdala, with little systematic damage to anterior medial amygdala or to adjacent structures. Lesion electrodes were withdrawn without current application in sham-operated animals (SHAM). After recovery for brain surgery, males were tested for (1) noncontact erection (NCE) that occurs when males were placed in proximity to inaccessible estrous females, (2) reflexive erection evoked in supine males by retraction of the penile sheath, and (3) copulatory behaviour with receptive females. In the NCE test, none of the MAL males showed penile erection during the 20 min observation, whereas 70% of the SHAM males showed it (P < 0.001). In contrast, no erectile dysfunction in the MAL males was detected in the other two tests. MAL males displayed more penile-body erections (flips) than SHAM males in the reflexive-erection test (P < 0.05). In the copulation test, most of the MAL males achieved intromission, but their intromission ratio, a partial measure of erectile function, was marginally lower than that of SHAM males (P = 0.051). MAL males had longer intervals between intromissions (P < 0.001); as a result, none of them ejaculated during the 20 min period that followed the first intromission. The results suggest that the posterior medial amygdala plays an essential role in the regulation of NCE, and it may also contribute to the regulation of erection in other contexts.

Amygdala↗
PubMed1997

Regulation by growth hormone-releasing hormone and somatostatin of a Na+ current in the primary cultured rat somatotroph.

The purpose of the present study is to characterize Na+ current activated by GH-releasing hormone (GHRH) and to investigate the effect of somatostatin (SRIF) on that current, because the Na+ current has been suggested to play a pivotal role in the process of GHRH-induced GH secretion. Primary-cultured pituitary somatotrophs were prepared from male Wistar rats. Whole-cell membrane currents were recorded and analyzed by a perforated patch clamp system. To isolate Na+ current, K+ and Ca2+ were replaced with Cs+ and Mg2+, respectively, in the extracellular solution, and cesium aspartate was used for the pipette solution. Furthermore, tetrodotoxin and nifedipine were added to the extracellular solution to eliminate the voltage-gated currents. Under these conditions, GHRH activated a mean inward Na+ current (-1.86 +/- 0.33 pA, mean +/- SE) at potentials between -50 and -20 mV and a smaller current (-0.59 +/- 0.13 pA) at potentials between -100 and -80 mV, which were completely blocked by protein kinase A blocker (H-89). In addition, SRIF (1-10 nM) partially suppressed these Na+ currents, which were not affected by phosphatase inhibitors (okadaic acid and calyculin A). These results suggest that GHRH activates the Na+ current through phosphorylation by protein kinase A and that SRIF partially suppressed this current and that the current was larger at more positive potentials than at more negative potentials.

Animals↗
PubMed1997

[A case of infant testicular tumor diagnosed ultrasonographically in the prenatal period].

We report a case of testicular tumor detected by ultrasonography during the prenatal period. Ultrasonography performed at 32 weeks of gestation showed that one testis was larger than the other. The right testis was markedly enlarged at 38 weeks of gestation. The heterogeneous echo pattern of the right testis suggested a testicular tumor. Right high orchiectomy was performed 3 months after birth. Pathological findings of the tumor were teratoma with mature and immature components according to the histological classification of testicular tumor. In Japan, this is the second case diagnosed in the prenatal period using ultrasonography.

Female↗
PubMed1997

[Studies on residual cardiovascular dysfunction in patients receiving long-term antihypertensive treatment of calcium channel blockers: with special reference to left ventricular hypertrophy, and impairments of left ventricular diastolic function and carotid arterial distensibility].

Residual cardiovascular dysfunctions including left ventricular hypertrophy, and impairment of left ventricular diastolic function and carotid arterial distensibility were investigated in hypertensive patients treated with calcium channel blockers for more than 1 year. Ultrasonographic examinations of the heart and carotid artery were performed in patients treated with calcium channel blocker alone for more than 1 year (n = 45) and in age-, sex- and weight-matched control subjects (n = 29). The following parameters were obtained: left ventricular mass index, cardiac diastolic function (A/E ratio) and carotid arterial distensibility (Distens). Hypertensive subjects were re-examined under the same conditions with the same parameters after 10 +/- 5 months. Patients with hypertension revealed no significant changes in these three parameters after 10 +/- 5 months Patients with left ventricular hypertrophy (n = 20) revealed significant impairments in diastolic function and carotid arterial distensibility (A/E = 1.42 +/- 0.25, Distens = 2.4 +/- 1.3% kPa) compared to those without left ventricular hypertrophy (n = 25) (A/E = 1.18 +/- 0.29, Distens = 3.8 +/- 1.7% kPa, p < 0.05). Patients without left ventricular hypertrophy had significantly impaired cardiovascular functions compared to the normal control group (A/E = 1.03 +/- 0.27, Distens = 6.3 +/- 2.2% kPa, p < 0.05, p < 0.01 respectively). Therefore, only reduction of blood pressure with calcium channel blocker may not be enough to improve cardiovascular organ damage, especially in patients with residual left ventricular hypertrophy, and such residual functional deteriorations must be corrected probably with another pharmaceutical modality.

Aged↗