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Biomedical subjects

A Miyake

Publications and source records attributed to A Miyake.

At least 199 records · Page 11Linked to original sources

Effects of nocturnal hyperprolactinemia on ovarian luteal function and galactorrhea.

To determine the effects of nocturnal hyperprolactinemia on luteal function and galactorrhea we studied six diurnal normoprolactinemic women with regular menstrual cycles. The diurnal serum levels of prolactin (PRL), luteinizing hormone (LH) and progesterone (Prog) and the nocturnal PRL levels at 1 h intervals were determined throughout the first menstrual cycle. Four of the women were nocturnally normoprolactinemic and two showed nocturnal hyperprolactinemia and low luteal progesterone values. In the second menstrual cycle, they were given metoclopramide (10 mg) at midnight before sleep every day, and their serum levels of PRL, LH and Prog were determined by the same protocol as in the first cycle. During treatment with metoclopramide, all the women showed nocturnal hyperprolactinemia, but their diurnal PRL levels remained within the normal range. Low luteal Prog values were observed in all of them and the peak LH levels decreased in all four nocturnally normoprolactinemic women. They had galactorrhea but neither of the nocturnally hyperprolactinemic women had galactorrhea. These results suggest that nocturnal hyperprolactinemia is a cause of luteal insufficiency and galactorrhea.

Adult↗

Purification of gonadotropes and intracellular free calcium oscillation. Effects of gonadotropin-releasing hormone and interleukin 6.

The intracellular free calcium concentration ([Ca2+]i) in single gonadotropes was measured with a calcium-sensitive fluorescent dye indo-1 or fura-2 and a digital imaging fluorescence microscopic system to determine how interleukin-6 (IL-6) increases release of gonadotropins. IL-6 induced an increase in the basal [Ca2+]i or the amplitude of spontaneous oscillation of [Ca2+]i in gonadotropes in a mixed population. Gonadotropin-releasing hormone (Gn-RH) induced a biphasic increase in [Ca2+]i, a transient increase, and then a prolonged increase. These effects were inhibited by the absence of extracellular calcium or pretreatment with calcium channel blockers, cobalt or nifedipine. Next, purified gonadotropes were prepared by fluorescence-activated cell sorting and argon laser treatment of the cells. Gonadotropes labeled with anti-luteinizing hormone antibody were sorted by fluorescence-activated cell sorting and then cultured as monolayers for 24-48 h. In this way, gonadotropes were concentrated from 5-10% to 70-85% from whole pituitary cells. After relabeling with anti-luteinizing hormone antibody, 100% purified gonadotropes were obtained by killing other types of cells with an argon laser. Gonadotropin-releasing hormone induced almost the same responses of [Ca2+]i in the purified cell population as in the mixed cell population, but IL-6 did not affect [Ca2+]i in the purified gonadotropes. These results suggest that IL-6 affects calcium mobilization in gonadotropes indirectly via paracrine pathways.

Animals↗

Short-term treatment with 17-beta estradiol enhances spontaneous [3H] dopamine release from cultured rat tuberoinfundibular neurons.

The effects of 17-beta estradiol (E2) on spontaneous [3H] dopamine ([3H]DA) release was investigated using primary cultured cells from the tuberoinfundibular region of rat hypothalamus, which includes DA neurons. [3H] DA uptake by the neurons in the presence of E2 at 10(-8) mol/l was similar to that by control cells. Pretreatment with E2 at 10(-9) mol/l or more resulted in dose-dependent increase in spontaneous [3H] DA release from the cultured hypothalamic cells. The spontaneous [3H] DA release reached almost a plateau on pretreatment with E2 at 10(-9) mol/l for 6 hours. Pretreatment with 1 nM E2 also enhanced DA release induced by 10 microM ionophore A23187. These results indicate that estrogen stimulates tuberoinfundibular DA neuronal activity.

Animals↗

The interferon family stimulates the secretions of prolactin and interleukin-6 by the pituitary gland in vitro.

The effects of interferon-alpha, interferon-beta 1 and interferon-gamma on the secretions of prolactin (PRL) and interleukin-6 by primary cultured rat anterior pituitary cells were examined. These three interferons caused dose-dependent increases in PRL secretion within 30 min, and dose-dependent stimulation of interleukin-6 were weaker than the effects of interleukin-1 and tumor necrosis factor-alpha. These results suggest that interferons regulate PRL secretion from the pituitary gland, and that there may be a pathway in which interferons stimulate PRL secretion through interleukin-6 release.

Analysis of Variance↗

Epidermal growth factor attenuates cell proliferation by down-regulating the transforming growth factor-beta receptor in the osteoblastic cell line MC3T3-E1.

We investigated the role of transforming growth factor beta 1 (TGF-beta 1) in growth regulation of the murine osteoblastic cell line, MC3T3-E1. We detected TGF-beta activity in the conditioned medium of MC3T3-E1 cells and its activity was increased by acid treatment of the bioassay system using CC1 64 cells. Northern blot analysis revealed the expression of TGF-beta 1 precursor messenger ribonucleic acid (mRNA). MC3T3-E1 cells possessed a single class of high affinity TGF-beta 1 receptor (2.8 x 10(4) sites per cell, Kd = 196 pM). Cross-linking studies revealed three specific TGF-beta receptors with molecular masses of 65, 95 and 280 kDa. Both TGF-beta and epidermal growth factor (EGF) stimulated [3H]-thymidine incorporation into cells. EGF decreased the number of TGF-beta receptor dose-dependently, and pretreatment of cells with 10 nM EGF attenuated cell growth by TGF-beta. All these data suggested that TGF-beta might be an autocrine growth factor in murine osteoblastic MC3T3-E1 cells and that EGF might modulate the growth of cells by down-regulating the TGF-beta receptor level.

Animals↗

Extensor tendon rupture due to osteoarthritis of the distal radio-ulnar joint.

Five cases of closed rupture of the finger extensor tendon due to osteoarthritis of the distal radioulnar joint were studied. Difficulty in extension began at the little finger and extended to the ring and long fingers. Pain and swelling in the dorsal aspect of the wrist preceded the tendon rupture. Osteoarthritic changes at the distal radio-ulnar joint were more severe than those at the radio-carpal and intercarpal joints. The distal end of the ulna showed the plus variant, as well as dorsal dislocation or subluxation. All patients underwent a tendon graft or tendon transfer, with excision of the distal ulna. The tendon rupture was thought to be caused mainly by friction between the displaced distal end of the ulna and osteophytes of the distal radio-ulnar joint.

Aged↗

Interleukin-6 stimulates gonadotropin-releasing hormone secretion from rat hypothalamic cells.

There are reports that both interleukin-1 beta and interleukin-6 (IL-6) stimulate the release of adrenocorticotropin through stimulation of hypothalamic corticotropin-releasing factor. We established a primary culture system for hypothalamic neurons producing gonadotropin-releasing hormone (GnRH) and examined whether IL-6 stimulated their GnRH secretion. We demonstrated immunohistochemically that some of these neurons contained GnRH-like immunoreactivity. In primary cultures of these GnRH neurons, we found that the calcium ionophore A23187 stimulated GnRH secretion in a dose- and time-dependent manner. These hypothalamic cells secreted IL-6 spontaneously, producing about 10 ng/l in 24 h, and their IL-6 secretion was significantly stimulated by E2 at 10(-9)-10(-8) mol/l. This stimulatory effect was observed within 3 h. IL-6 also stimulated the release of GnRH in a dose- and time-dependent manner, and these effects of IL-6 were significantly blocked by anti-IL-6 antiserum. These results suggest that the central action of IL-6 on the GnRH neurons may be an important physiological event in the hypothalamus.

Animals↗

Effect of prolactin on the secretion of hypothalamic GnRH and pituitary gonadotropins.

In order to clarify the mechanism by which excess PRL inhibits gonadotropin release, in vivo and in vitro studies were performed with adult female rats. First, we examined the effect of hyperprolactinemia, produced by implantation of anterior pituitary glands under the kidney capsule, on catecholamine turnover in the medial basal hypothalamus (MBH) and on GnRH concentrations in MBH and hypophyseal portal blood. Rats bearing pituitary transplants exhibited increased turnovers of dopamine (DA) in the MBH, decreased concentrations of GnRH in the MBH and in plasma of hypophyseal portal blood and impaired gonadotropin release from the pituitary gland. Second, we examined the effects of PRL on DA release and of DA on GnRH release from rat hypothalamic cells. We observed that PRL stimulated [3H] DA release, and DA inhibited ionophore-induced GnRH release from dispersed hypothalamic cells. Third, we examined the effect of PRL on estrogen-induced LH release using the in vitro perfusion system. We found that administration of PRL suppressed estrogen-induced LH release by suppressing GnRH release from the hypothalamus. These findings suggest that chronic hyperprolactinemia may increase dopaminergic tone in the MBH that may inhibit GnRH secretion from the MBH and LH release from the pituitary and that these processes may be responsible for disturbances of cyclic hypothalamic pituitary-ovarian activity.

Animals↗

Tumor necrosis factor-alpha stimulates prolactin release from anterior pituitary cells: a possible involvement of intracellular calcium mobilization.

We investigated the effects of tumor necrosis factor-alpha (TNF alpha), a cytokine produced as one aspect of inflammatory reactions, on the intracellular free calcium concentration in single pituitary cells using a calcium-sensitive fluorescent dye, indo-1, and a digital imaging fluorescence microscopic system. TNF alpha induced an increase in intracellular free calcium immediately after administration, reaching a peak after 30 sec and then returning to nearly the basal level after 120 sec in the pituitary cells. The cells responding to TNF alpha constitute about 15% of the pituitary cell population, and these cells never responded to the hypothalamic releasing hormones TRH, GnRH, GH-releasing hormone, or CRH. To define the role of calcium in TNF alpha-induced PRL release, dispersed pituitary cells were exposed to agents that modify TNF alpha-induced calcium mobilization. Such calcium channel blockers as cobalt and verapamil decreased basal and TNF alpha-induced PRL release. A low calcium medium also decreased TNF alpha-induced PRL release. These data suggest that intracellular calcium mobilization may be involved in the process of TNF alpha-induced PRL release.

Animals↗

Tumor necrosis factor-alpha increases release of arachidonate and prolactin from rat anterior pituitary cells.

We investigated the effect of tumor necrosis factor-alpha (TNF alpha), a product of activated macrophages, on the release of arachidonate from dispersed anterior pituitary cells. Primary cultures of anterior pituitary cells from rats were preincubated with [3H]arachidonate to label their phospholipid-containing components. The cells were then washed and incubated with vehicle or test agents, and PRL release into the medium and [3H]arachidonate cleaved from phospholipid were measured. TNF alpha significantly increased the release of both PRL and [3H] arachidonate release in a time- and dose-dependent manner. Other cytokines, such as interleukin-1 alpha, interleukin-1 beta, and gamma-interferon, had no effect on [3H]arachidonate release. To define the role of calcium in TNF alpha-induced arachidonate release, dispersed pituitary cells were incubated with low calcium medium, which decreased arachidonate release in response to TNF alpha. TNF alpha potentiated the release of [3H]arachidonate and PRL promoted by phospholipase-A2 and melittin, and markedly shifted the dose-response curve to the left. Inhibitors of phospholipase-A2, such as p-bromophenacyl bromide and quinacrine, had no effect on TNF alpha-induced [3H]arachidonate and PRL release. BW755C, an inhibitor of the conversion of arachidonate to its metabolites, decreased TNF alpha-induced PRL release, while indomethacin, a prostaglandin synthesis inhibitor, had no effect on TNF alpha-induced PRL release. These data indicate that arachidonate metabolites may be involved in the process of TNF alpha-induced PRL release.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

Decrease in epidermal growth factor receptor and its messenger ribonucleic acid levels in intrauterine growth-retarded and diabetes mellitus-complicated pregnancies.

We measured the amounts of epidermal growth factor receptor (EGFR) in plasma membranes from human placentas at term delivery in three groups: appropriate for gestational age (AGA), intrauterine growth-retarded (IUGR), and diabetes mellitus-complicated (DM) pregnancies. At the same time, EGFR mRNA levels were examined in three groups by dot and Northern blot analyses. Binding studies were performed using 125I-labeled human EGF as a ligand, and two classes (high and low) of binding sites were found in all specimens. Although dissociation constants (Kd) were not significantly different among three groups, the number of binding sites was significantly decreased in IUGR and DM placentas compared to that in the AGA group. Total cellular RNA was isolated from a part of the placentas used for binding studies using the guanidinium CsCl method, denatured, and dot blotted onto nitrocellulose filter. Poly(A)+ RNA was selected from the total RNA, electrophoresed in 1% agarose gel, and transferred onto nitrocellulose filters. Then, hybridization with 32P-labeled pE7 (a cDNA of EGFR), autoradiography, and densitometry were performed. The amounts of mRNA hybridized with pE7 were reduced in IUGR and DM placentas compared to that in the AGA group. The molecular sizes of EGFR mRNA were 10 and 5.6 kilobases in all three groups. These results suggest possible physiological actions of EGF on adequate feto-placental growth and development in human pregnancy.

Diabetes Mellitus↗

Effect of TNF-alpha on prolactin secretion from rat anterior pituitary and dopamine release from the hypothalamus: comparison with the effect of interleukin-1 beta.

The effects of human recombinant interleukin-1 beta and -6 and tumor necrosis factor-alpha (TNF-alpha) on the releases of PRL and dopamine were examined using monolayer cultures of rat pituitary cells and hypothalamic cells. The release of PRL from rat pituitary cells in 30 min was increased about 2-fold (p less than 0.05) by 10(5) U/l interleukin-1 beta, 10(5) U/l interleukin-6 or 100 micrograms/l TNF-alpha. TNF-alpha at 100 micrograms/l significantly increased PRL release within 5 min incubation and this effect continued throughout the next 30 min of incubation. Incubation for 5 min with TNF-alpha caused dose-dependent stimulation of PRL release. These cytokines did not modulate [3H]-dopamine release from primary cultures of hypothalamic cells. These results suggest that these cytokines stimulate PRL release directly at the pituitary gland, without modifying the release of dopamine from the hypothalamus.

Animals↗

Studies on condensed-heterocyclic azolium cephalosporins. I. Synthesis and antibacterial activity of 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)- alkoxyiminoacetamido]-3-(imidazo[1,2-a]pyridinium-1-yl)methyl-3- cephem-4-carboxylates.

In our study of the structure-activity relationships of cephalosporins bearing quaternary ammonium groups at the 3 position, we postulated that delocalization of the azolium positive charge would lead to an expanded antibacterial spectrum and increased activity. Since quaternization of condensed-heterocyclic compounds such as imidazo[1,2-a]pyridine gives positive charge delocalization, 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-alkoxyiminoacetamido] cephalosporin derivatives (1-53) bearing various (imidazo[1,2-a]pyridinium-1-yl)methyl moieties at the 3 position were prepared and their antibacterial activity was determined. As expected, these cephalosporins exhibited potent activity against both Gram-positive and Gram-negative bacteria including Pseudomonas aeruginosa. These results imply that imidazo[1,2-a]pyridine is a quite useful substituent for improving antibacterial activity and spectrum. The structure-activity studies revealed that a favorable substituent on the imidazo[1,2-a]pyridine is the cyano radical at the 6 position of the ring, and ethoxyimino or 1-carboxy-1-methylethoxyimino groups are suitable for the alkoxyimino substituent. Among the cephalosporins tested, 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)- ethoxyiminoacetamido]-3-(6-cyanoimidazo[1,2-a]pyridinium -1-yl)methyl-3-cephem-4-carboxylate (45) and 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-(1- carboxy-1-methylethoxyiminoacetamido]-3-(6-cyanoimidazo[1,2- a] pyridinium-1-yl)methyl-3-cephem-4-carboxylate (49) showed good antibacterial activity.

Cephalosporins↗

Studies on condensed-heterocyclic azolium cephalosporins. II. Synthesis and antibacterial activity of 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-alkoxyiminoacetamido]-3-(condensed- heterocyclic azolium)methyl-3-cephem-4-carboxylates.

From our series of studies on cephalosporins bearing condensed-heterocyclic azolium methyl groups at the 3 position in the cephalosporin nucleus, we describe here the synthesis and antibacterial activity of 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-alkoxyiminoacetamido]ceph alosporins containing imidazo[1,5-a]pyridinium, imidazo[1,2-b]pyridazinium, imidazo[1,2-a]pyrimidinium, imidazo[1,2-c]pyrimidinium, and pyrazolo[1,5-a]pyridinium methyl groups at the 3 position. Among the cephalosporins tested, 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido]-3- (imidazo[1,5-a]pyridinium-2-yl) (1), (imidazo[1,2-b]pyridazinium-1-yl) (2), and (pyrazolo[1,5-a]-pyridinium-1-yl) (3)methyl-3-cephem-4-carboxylates showed potent antibacterial activity and broad antibacterial spectrum. The antibacterial activity of these cephalosporins (1 approximately 3) was superior to that of ceftazidime (CAZ). These results imply that the delocalization of the positive charge of the imidazo[1,5-a]pyridinium, pyrazolo[1,5-a]pyridinium and imidazo[1,2-b]pyridazinium groups leads to an expanded antibacterial spectrum and increased activity and that these condensed-heterocyclic compounds as well as imidazo[1,2-a]pyridine are effective moieties for improving antibacterial activity and spectrum.

Cephalosporins↗

[Re-evaluation of hysteroscopy in the diagnosis of uterine endometrial cancer].

To evaluate the clinical value of hysteroscopy in the management of endometrial cancer, findings in 3,681 patients with endometrial cancer treated between 1985 and 1989 at 167 hospitals in Japan were analyzed. In 1,040 of these patients, hysteroscopy was performed before operation. Pre-operative staging by fractional curettage with or without hysteroscopy was compared with post-operative histological diagnoses. The accuracy rates of diagnosis at final stages I and II were 91.4% and 79.4%, respectively, with hysteroscopy. There figures were not significantly different from those of 91.4% and 77.7% without hysteroscopy. The accuracy rate for diagnosis at the final stage I was 98.0% with the hystero-fiberscope and significantly higher than that with rigid hysteroscopy (86.0%). Tumor cells in the pelvic cavity were examined at the time of operation in 1,115 patients. Tumor cells were found in 8.5% of those in stage I, 18.8% of those in stage II, 64.7% of those in stage III and 75.0% of those in Stage IV by hysteroscopy. These values were not significantly different from those of 7.3%, 22.7%, 57.1% and 81.1%, respectively, observed without hysteroscopy. These findings indicate that hystero-fiberscopy might be valuable for the pre-operative diagnosis of endometrial cancer, but has no effect on cytological malignancy in the peritoneal cavity.

Adult↗

[A case of multiple pulmonary arteriovenous fistulae associated with splenic abscess].

A 51-year-old female was admitted with high grade fever, cyanosis and hypoxemia. The chest X-ray showed nodular shadows on bilateral lung fields. Beta-streptococci were found on culture from the blood, and the fever fell after administration of both antibiotics and corticosteroid. Pulmonary angiography revealed four arteriovenous fistulae on bilateral lung fields. On abdominal ultrasonography and CT scan, a hypoechoic lesion with an irregular wall and varying internal echogenicity was detected within the spleen. This lesion changed in size and shape during the clinical course and diminished with improvement in the patient's condition. These findings were compatible with splenic abscess. Splenic abscess with pulmonary arteriovenous fistulae is rare.

Abscess↗

[A case of pulmonary alveolar microlithiasis showing respiratory failure after 33 years and revealing microliths in bronchoalveolar lavage].

A 43-year-old woman was admitted to our hospital because of dyspnea and anorexia. She had hypoxia and cyanosis. The chest roentgenogram revealed dense reticular, partly nodular shadow and emphysematous bullae in both lung fields. An abnormal chest X-ray had been pointed out and pulmonary alveolar microlithiasis had been diagnosed 33 years previously. Bronchoscopy and bronchoalveolar lavage were performed and calcium microliths were seen in the bronchoalveolar lavage fluid smear. Bronchoalveolar lavage appears useful in the diagnosis of pulmonary alveolar microlithiasis. A series of X-ray findings showed development of emphysematous bullae, niveau formation and disappearance of bullae. These changes seem to reveal the progress of her disease from the established stage to the advanced stage. Such a case of pulmonary alveolar microlithiasis over the course of a long period is rare.

Adult↗

[A case of apyretic miliary tuberculosis which was discovered accidentally].

A 78 year-old female was referred to our hospital, because diffuse miliary shadows in bilateral lung fields were discovered during upper G.I. series. She did not complain of fever or display any chest symptoms. Her laboratory data on admission revealed mild hypoxemia and high serum CA 19-9. The transbronchial lung biopsy specimen proved epithelioid cell granulomas. M. tuberculosis was observed on culture from the sputa, urine and bronchoalveolar lavage fluid. She was diagnosed to have miliary tuberculosis, and antituberculous drugs were administered. After the antituberculous therapy, the diffuse miliary shadows on the chest X-ray diminished gradually, and the laboratory data improved. No elevation in the body temperature was seen during the entire clinical course. Though it is known that miliary tuberculosis in elderly patients is often atypical and has mild symptoms, miliary tuberculosis without fever is very rare.

Age Factors↗