Cytochemical demonstration of guanase in human liver using yellow tetrazolium.

Histochemical studies of human guanase (guanine deaminase) have seldom been undertaken, in part because of technical difficulties which result in heavy background staining. We reported a modified procedure for histochemical demonstration of guanase in human tissues involving hydrolytic deamination of the substrate guanine to xanthine via guanase, and then oxidation of xanthine to uric acid, with concomitant reduction of nitrotetrazolium blue (NBT). In this report, we describe a modification of this method for cytochemical demonstration of guanase at the fine structural level using yellow tetrazolium in place of NBT for determination of the intracellular distribution of guanase in human hepatocytes.

Growth inhibition by danazol in a human endometrial cancer cell line with estrogen-independent progesterone receptors.

Since we recently found that danazol, an isoxazol derivative of ethinyltestosterone, has a growth-inhibitory effect on human endometrial cancer cells in primary culture, the effects of danazol on a human endometrial cancer cell line (IK-90 cells), which contains estrogen-independent progesterone receptors (PR), were investigated in the present study. The addition of danazol (1 nM-1 microM) in culture medium caused a decrease in the growth of IK-90 cells in a dose-dependent manner. Competitive binding studies showed that danazol effectively binds to PR in IK-90 cells, and the binding affinity for PR was estimated to be 6.

Effect of the enteroinsular axis on both the A- and B-cell response to arginine after oral glucose in man.

Studies were made on the effect of the enteroinsular axis on amino acid-induced insulin and glucagon secretion during hyperglycaemia in man. The responses of plasma immunoreactive insulin, C-peptide, and immunoreactive glucagon to arginine infusion were investigated in nine healthy subjects after induction of hyperglycaemia by an oral glucose load and by intravenous glucose infusion to produce similar glucose concentrations in the arterialised blood. The plasma immunoreactive insulin and C-peptide levels increased to higher levels after an oral glucose load than after an intravenous infusion of glucose.

Identification and localization of glucagon-like peptide-1 and its receptor in rat brain.

The existence and distribution of glucagon-like peptide-1 (GLP-1) and its receptor in rat brain in relation to that of glucagon were examined. The concentration of GLP-1 immunoreactivity (GLP-1-IR), measured by a specific and sensitive RIA established in this study with anti GLP-1 serum (LMT-01), was found to be highest in the thalamus-hypothalamus, followed by the medulla oblongata. The distribution of glucagon-like immunoreactivity was similar to that of GLP-1-IR.

A large molecular form of glucagon-like peptide-1 (GLP-1) immunoreactivity is co-released with glucagon from pancreas by arginine in normal subjects.

Plasma immunoreactivities of glucagon-like peptide-1 (GLP-1IR) in normal subjects were measured with a specific radioimmunoassay during the arginine tolerance test. Plasma GLP-1IR after arginine infusion showed a 3-fold increase in parallel to plasma glucagon immunoreactivity and plasma glucagon-like immunoreactivity, measured with a glucagon C-terminal specific antiserum (OAL 123) and an N-terminal and/or central region specific glucagon antiserum (OAL 196), respectively. This finding suggested that the increased immunoreactivities of GLP-1 as well as that of glucagon were of pancreatic origin.

Roles of antiestrogen binding sites in human endometrial cancer cells.

Estrogen-noncompatible antiestrogen binding sites (AEBS) as well as estrogen receptors (ER), and the growth-inhibitory effect of tamoxifen were investigated in two human endometrial cancer cell lines, IK-90 and HEC-IA cells. IK-90 cells contained specific AEBS, but no ER was found in these cells. Scatchard plot analysis of AEBS in 12,000 g supernatant from IK-90 cells showed a high affinity binding site for tamoxifen (Kd:5.

Growth inhibition by progestins in a human endometrial cancer cell line with estrogen-independent progesterone receptors.

The presence of estrogen-independent progesterone receptors (PgR) was demonstrated in a subline of a human endometrial cancer cell line, Ishikawa cells, although the original Ishikawa cells contained estrogen-inducible PgR. Scatchard plot analysis of cytoplasmic binding data in our subline (IK-90) revealed a high affinity binding site for R5020 (Kd, 1.0 nM) with maximum binding sites of 158 fmol/mg protein.

Effects of gut hormones on bile acid uptake and release in cultured rat hepatocytes.

In cultured rat hepatocytes, the effects of gut hormones on bile acid uptake and release were studied. It was found that cultured hepatocytes continued to secrete bile acids into the culture medium and incorporated them effectively as a function of incubation time. Gut hormones such as secretin, glucagon, vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), gastric inhibitory polypeptide (GIP), tetragastrin, cholecystokinin-octapeptide (CCK-8), pancreatic polypeptide (PP), neurotensin substance P, beta-endorphin (beta-End), methionine-enkephalin (Met-enk), motilin, bombesin and somatostatin (SS) had no effect on bile acid uptake by cultured hepatocytes.

Neuroeffector function in mesenteric arteries isolated from beagles of different ages.

In helical strips of mesenteric arteries from 30-day (28-35 day), 3-month (80-110 day), 2-year (10-40 month) and 12-year (135-161 month)-old beagles, contractile responses to vasoconstrictors were compared. The responses to transmural stimulation and norepinephrine, relative to those caused by 30 mM K+, were greater in the infant beagle arteries than in those from the older beagles. Equipotent concentrations of the amine for producing the same magnitude of contraction as that evoked by 5 or 20 Hz stimulation in beagles of different ages did not differ.

Beta-endorphin in the human gallbladder.

The presence of beta-endorphin-like immunoreactivity (beta-END-LI) in human gallbladder and its release were examined by means of radioimmunochemical measurements and immunohistochemical stainings. beta-END-LI was detected in the gallbladder (27.2 +/- 3.

Alterations with age of the response to vasodilator agents in isolated mesenteric arteries of the beagle.

Responses to vasodilator agents were compared in helical strips of mesenteric beagles of different ages (30 days, 3 months, 2 years and 12 years old), precontracted with prostaglandin F2 alpha (PGF2 alpha). Relaxations induced by isoprenaline and adenosine were related inversely to age, whereas those induced by PGI2 and K+ (5 mM) did not alter with age. Acetylcholine-induced relaxations were less in the arteries from the aged (12 year old) beagles than in those from the younger beagles.

Danazol binds to progesterone receptors and inhibits the growth of human endometrial cancer cells in vitro.

Based on our recent findings that danazol, an isoxazol derivative of ethinyltestosterone, has a profound growth-inhibitory effect on an established human endometrial adenocarcinoma cell line, the effects of danazol on cancer cells from human endometrial adenocarcinomas obtained by hysterectomy were investigated in the present study. Of the 22 uterine adenocarcinomas, estrogen, progesterone, and androgen receptors were found in 12, 14, and 4 tumors, respectively. Competitive binding studies showed that danazol specifically binds to progesterone and androgen receptors but not to estrogen receptors.

Responsiveness to vasoconstrictor and dilator agents of senescent beagle cerebral arteries.

With advancing age from 2 to 12 years, contractions of isolated beagle cerebral arteries mediated by histamine H1 and serotonin receptors increased, whereas those induced by noradrenaline and angiotensin II did not differ. Relaxations by vasodilator substances, such as prostaglandin (PG) I2, isoproterenol, adenosine and K+ (5 mM), and by stimulation of vasodilator nerves in the adult and senescent beagle arteries did not significantly differ.

Age-dependent change in the response of isolated beagle cerebral arteries to vasoactive agents.

Responses to vasoactive agents were compared in helical strips of cerebral arteries from beagles of different ages (30 days, 3 months, 1 year, and 3 years old). Contractile responses to norepinephrine, serotonin, and histamine, relative to those induced by 30 mM K+, were greater in the infant (30-day-old) beagle arteries than in those from the older beagles. Angiotensin II-induced contractions did not differ in these arteries, whereas relaxations induced by the peptide, converted to contractions by indomethacin, were greater in the arteries from adult beagles than in the immature beagle arteries.

Dexamethasone inhibits the effects of oestrogen on the pituitary gland in rats.

The administration of glucocorticoids has been shown to be effective for the induction of ovulation in patients with anovulation. In the present study, we investigated the effects of a glucocorticoid on oestrogen-induced changes in the pituitary gland. A single ip injection of 10 micrograms oestradiol-17 beta (E2) in ovariectomized and adrenalectomized rats resulted in a significant increase in pituitary weight and progesterone receptor (PgR) concentration.

Concentrations of metallothionein and metals in malignant and non-malignant tissues in human liver.

Concentration of metallothionein in the malignant and non-malignant tissues of the human liver was determined by the Cd-hem method. The concentration of metallothionein was high in the non-malignant tissue (471 +/- 306 micrograms/g). Metallothionein in the non-malignant tissue was mainly Zn-thionein and metallothionein-bound Zn was a major chemical form of Zn in the non-malignant tissue.

Analysis of ouabain-induced contractions in isolated coronary arteries.

Contractile responses to ouabain in helical strips of dog and monkey coronary arteries were investigated. Ouabain (5 X 10(-8) to 5 X 10(-6) M) caused a dose-related contraction in dog and monkey arteries; the response of monkey coronary arteries was significantly greater. In dog coronary arteries, contractile responses to high concentrations of ouabain were potentiated by treatment with propranolol.

Clomiphene citrate induces pituitary GnRH receptors in ovariectomized rats: its possible role in induction of ovulation.

Since our previous studies have shown that clomiphene citrate (clomiphene) acts directly on the pituitary gland and exerts a facilitatory role on oestradiol-17 beta (E2)-induced LH surge in chronically ovariectomized rats, the effect of clomiphene on pituitary GnRH receptors was investigated. A single ip injection of either 5 micrograms E2 or 200 micrograms clomiphene did not induce LH release in adult rats ovariectomized 1-2 weeks before the injection. However, a significant increase in serum LH was noted 24 h after a single injection of E2 in the ovariectomized rats, if clomiphene was pre-injected 48 h before the E2 injection.

An elevated type of gastric ulcer scar in patients treated with cimetidine.

An elevated type of gastric ulcer scar (EUS) (A) was noted in 8 out of 227 ulcer patients treated with cimetidine. These were compared with 15 patients with EUS (B), not treated with cimetidine and the etiology of the lesion was discussed. The incidence of EUS (3.

[In vivo and in vitro effects of bradykinin on the release of beta-endorphin-like immunoreactivity].

The effect of bradykinin (BK) on the release of beta-endorphin-like immunoreactivity (beta-END-LI) in rats was studied in in vivo and in vitro. Intraperitoneal injection of BK at 5 micrograms/100 g body weight resulted in a significant increase in the plasma beta-END-LI level after 15 min. BK at concentrations of 10(-12)-10(-7) M also caused dose-dependent stimulation of beta-END-LI release from the dispersed cells of the anterior pituitary of rats.

Postmortem functional changes in coronary and cerebral arteries from humans and monkeys.

Contractile responses to 30 mmol . litre-1 K+ of helical strips of coronary arteries from human cadavers did not change within 5 h after death; however, they were suppressed 8 h after death. In coronary arteries from monkey cadavers, the K+-induced contractions did not significantly differ within the first 5 h, but were suppressed 12 h after death.

Dexamethasone suppresses estrogen action at the pituitary level without modulating estrogen receptor dynamics.

The administration of glucocorticoid combined with antiestrogen such as clomiphene has been shown to be effective for the induction of ovulation in patients with anovulation. The present study was undertaken to examine the effects of glucocorticoid on estrogen-induced changes in the pituitary gland. A single intraperitoneal (i.

Decrease of LRH receptors in the pituitary gland in streptozotocin-induced diabetic rats.

In studies into the mechanism of anovulation in the diabetic condition, the LRH receptor content of the pituitary gland of rats with diabetes mellitus was determined. Normal female rats weighing 180-200 g were injected iv with either streptozotocin (6 mg/100 g body weight) or vehicle in dioestrus of the oestrous cycle. The rats were sacrificed by decapitation 9 days after treatment, and serum LH concentrations and the LRH content of the medial basal hypothalamus (MBH) were measured by radioimmunoassay (RIA), and the LRH receptor content of the pituitary gland was determined.