Biomedical subjects

Y Ueta

Publications and source records attributed to Y Ueta.

At least 109 records · Page 6Linked to original sources

PubMed1995

Water deprivation in the rat induces nitric oxide synthase (NOS) gene expression in the hypothalamic paraventricular and supraoptic nuclei.

We examined the effects of water deprivation on nitric oxide synthase (NOS) gene expression in the rat hypothalamic paraventricular (PVN) and supraoptic nuclei (SON), using in situ hybridization histochemistry. Dehydration caused a significant increase in NOS gene transcripts in the PVN and SON but not in the subfornical organ (SFO). The results suggest that dehydration has a major effect on the NOS gene expression in the PVN and SON.

Animals↗

PubMed1995

Activity of neurons in the lateral preoptic area during drinking behavior by the rat.

Rats were trained to drink water, sucrose solution, and saline while their heads were painlessly held in a stereotaxic apparatus with an attachment fixed to the skull. A total of 286 neurons in the lateral preoptic area (LPO) were recorded during the drinking behavior. During water intake, 40% of the neurons tested were either excited or inhibited. Sucrose elicited responses in 25% of the neurons, and saline in 34%. Of the 52 neurons recorded while rats drank all test solutions, 8 specifically responded to water, 3 were sucrose specific, 4 were saline specific, 12 responded to all solutions, and the remaining 25 did not respond to any solutions. Artificial cerebrospinal fluids (ACSFs) with physiologically hypertonic (+30 mOsm/kg, by NaCl or mannitol) and hypotonic (-30 mOsm/kg) osmotic pressure were applied to 88 neurons through a multibarrel micropipette. Of these neurons, 15 (17%) were hypotonic-sensitive; they were excited by hypotonic ACSF and/or inhibited by hypertonic ACSFs. There were 4 (5%) that were hypertonic-sensitive; they were excited by hypertonic ACSFs and/or inhibited by hypotonic ACSF. Of six hypotonic-sensitive neurons examined, three were water specific, and none were sucrose nor saline specific. Of four hypertonic-sensitive neurons, one was water specific, and another was saline specific. These results showed activity of some LPO neurons specifically related to water intake. Osmosensitive neurons in the LPO may regulate water intake.

Action Potentials↗

PubMed1995

Osmosensitive hypothalamic neurons and their responses to cardiovascular receptor activation.

Neurons in the rostral hypothalamic areas were examined with physiologically hypertonic (+30 mOsm/kg, by NaCl or mannitol) and hypotonic (-30 mOsm/kg) artificial cerebrospinal fluids (ACSFs) applied by pressure through a multibarrel micropipette in urethane-anesthetized rats. Of 304 neurons tested, 39 were excited by the hypertonic ACSFs and/or inhibited by the hypotonic ACSF, and 35 were inhibited by the hypertonic ACSFs and/or excited by the hypotonic ACSF. The former cells were designated hypertonic-sensitive and the latter hypotonic-sensitive. Both types of osmosensitive neurons were diffusely scattered in the examined areas, but neurons in the lateral preoptic area and the bed nucleus of the stria terminalis responded more frequently (30-40%) to the osmotic stimuli. Osmosensitive and insensitive neurons were recorded during activation of the baro- and volume receptors of the cardiovascular system. Of seven neurons that were excited during temporal hypotension induced by intravenous administration of nitroprusside, five were hypertonic-sensitive and two were osmotically insensitive. Hypertonic-sensitive neurons may be activated during dehydration, which increases the osmotic pressure and decreases the volume of body fluids. Of six neurons that were excited during temporal hypertension induced by intravenous administration of phenylephrine, four were hypotonic-sensitive and two were osmotically insensitive. Hypotonic-sensitive neurons may be activated during rehydration or overhydration. Osmosensitive neurons probably integrate cardiovascular and osmotic information that is important for the central regulation of body fluids.

Action Potentials↗

PubMed1995

A patient with an autonomously functioning thyroid nodule with papillary adenocarcinoma associated with Graves' hyperthyroidism.

A 69-year-old man had concomitant findings of an autonomously functioning thyroid papillary adenocarcinoma and Graves' hyperthyroidism. The patient presented with hyperthyroidism and a right lobe thyroid nodule that was shown to be hyperfunctional on I-123 imaging. The TI-201 imaging showed uptake confined almost entirely to the right lobe nodule. Papillary adenocarcinoma in the nodule and diffuse hyperplasia surrounding the nodule along with a slightly enlarged left lobe were found at surgery.

Adenocarcinoma, Papillary↗

PubMed1995

Inhibition of hypothalamic nitric oxide synthase gene expression in the rat paraventricular nucleus by food deprivation is independent of serotonin depletion.

We have investigated the effects of food deprivation on nitric oxide synthase (NOS) transcript levels in the rat paraventricular (PVN) and supraoptic nuclei (SON), using in situ hybridization histochemistry. Food deprivation for 48 h significantly and consistently reduced NOS transcript prevalence by approximately 50% in both sites. Since there is considerable evidence for an important role of 5-HT in feeding behaviour, we then examined the effect of food deprivation on NOS gene expression in the PVN following para-chlorophenylalanine (PCPA)-induced hypothalamic 5-HT depletion. As starvation causes central down-regulation of the thyroid axis, changes in thyrotropin-releasing hormone (TRH) and pituitary thyrotrophin (TSH) transcript prevalence were used as internal controls. PCPA pretreatment (200 mg/kg body weight as a single daily dose ip for 2 days) had no significant effect on basal levels of NOS, TRH or TSH transcripts, or on the effect of a subsequent 48 h fast, which significantly reduced all three. These results show for the first time, that food deprivation for 48 h significantly reduces NOS gene expression in the rat PVN and SON. Secondly, that basal levels and the fasting-induced reductions in the prevalence of NOS, TRH and TSH transcripts were not affected by PCPA-induced hypothalamic 5-HT depletion. Therefore, at least under the experimental conditions used here, 5-HT does not appear to be involved in setting baseline levels- or in the starvation-induced inhibition of NOS or thyroid axis gene expression in the PVN.

Animals↗

PubMed1995

S-100 antigen-positive folliculostellate cells are not the source of IL-6 gene expression in human pituitary adenomas.

We have investigated the expression of IL-6 in a random selection of 27 human pituitary adenomas, comprising 8 somatotroph, 5 corticotroph, 3 mammotroph and 11 endocrinologically inactive adenomas, using a 35S-labelled 1.1kb riboprobe complementary to human IL-6. Positive and negative IL-6 transcript controls were generated from the IL-6-secreting human bladder carcinoma cell line T24/83. Tissue from a malignant melanoma was used as a positive S-100 immunocytochemical control tissue. Of the 27 human pituitary adenomas examined by in situ hybridization, 7 (26%) contained IL-6 transcripts: these were 3 of 5 corticotroph adenomas, 2 of 8 somatotrophinomas and 2 of 11 endocrinologically inactive adenomas. In each case, IL-6 transcript-positive cells constituted less than 1% of the total pituitary tissue mass examined. Alternate wax embedded 3 microns thick sections from 5 of the 7 IL-6 transcript positive tumours were examined immunocytochemically for S-100 antigen, or by in situ hybridization for IL-6 transcripts. Immunocytochemistry for S-100 antigen was completely negative in 3 of the 5 tumours and in the remaining 2, there was no evidence of IL-6 transcripts and S-100 antigen co-localization in any of the sections examined. This suggests that in pituitary adenomas, cells other than classical folliculostellate cells are responsible for IL-6 production.

Adenoma↗

PubMed1995

Hypothalamic nitric oxide synthase gene expression is regulated by thyroid hormones.

We investigated the effects of thyroid status on nitric oxide synthase (NOS) gene expression in the rat hypothalamic paraventricular (PVN) and supraoptic nuclei (SON). Propylthiouracil (PTU)-induced hypothyroidism in male rats produced a highly significant reduction in NOS gene transcripts in the PVN and SON, as assessed by quantitative in situ hybridization histochemistry with a specific oligodeoxynucleotide probe. The addition of T3 (40 micrograms/kg) to the PTU-containing diet completely prevented the reduction in NOS transcripts. Hyperthyroidism, induced by adding 160 micrograms/kg T3 to the food, more than doubled the prevalence of NOS transcripts in the PVN and SON after a similar time. Up-regulation of NOS gene transcripts induced by the osmotic stimulus of chronic salt loading was markedly attenuated by PTU-induced hypothyroidism. These results demonstrate a major effect of thyroid status on regulation of NOS gene expression in the hypothalamus.

Amino Acid Oxidoreductases↗

PubMed1995

Development of hypercalcemic crisis in a Graves' hyperthyroid patient associated with central diabetes insipidus.

A 26-year-old man with Graves' hyperthyroidism associated with central diabetes insipidus (DI), initially showed hypercalcemic crisis. Initially, very low serum levels of intact parathyroid hormone (PTH) and 1,25-dihydroxy vitamin D3 and a moderate rise of serum C-terminal PTH related protein (C-PTHrP) were observed which strongly suggested a humoral hypercalcemia of malignancy due to PTHrP. However, the serum C-PTHrP level later became normal. Mild hyperprolactinemia, no responses of growth hormone (GH) to insulin-induced hypoglycemia despite a normal growth hormone releasing hormone (GRH) test and mild thickening of the pituitary stalk on magnetic resonance imaging were observed. Thus, an autoimmune nature of his central DI is considered; it is noteworthy that the serum C-PTHrP level may be elevated by renal failure in patients with hypercalcemia due to causes other than PTHrP.

Acute Disease↗

PubMed1995

Does recurrent inhibition exist in the paraventricular magnocellular neurosecretory cells in the male rat?

Extracellular recordings were performed from the paraventricular (PVN) neurosecretory cells in the anesthetized male rats. After sub- and suprathreshold stimulations to the neural stalk, two of 38 neurons showed inhibitory phases and eleven of the remaining 36 neurons showed inhibitory responses after suprathreshold stimulations. These results indicate that the recurrent inhibitory system exists in the PVN.

Action Potentials↗

PubMed1995

Antiarrhythmic drugs inhibit the G-protein and K+ channels in the cultured thyroid cell line.

We examined the effects of antiarrhythmic drugs on the induction of cAMP by TSH (thyroid-stimulating hormone), using continuously cultured FRTL-5 rat thyroid cells. Group Ia antiarrhythmic drugs had no effect, but Group Ib antiarrhythmic drugs suppressed cAMP induction by TSH. These drugs suppressed cAMP induction in response to cholera toxin but did not inhibit TSH receptor binding or cAMP induction by forskolin. These results indicate that Group Ib antiarrhythmic drugs inhibit thyroid G-protein, resulting in a decrease in cAMP induction by TSH. We also examined the effect of antiarrhythmic drugs on K+ channels. Group Ia antiarrhythmic drugs had no effect on K+ channel activation by TSH and cAMP. On the other hand, Group Ib antiarrhythmic drugs suppressed K+ channel activation by TSH and cAMP. This indicates that the mechanism of suppression is not inhibition of TSH receptors or G-proteins but the direct suppression of K+ channels. Group Ib antiarrhythmic drugs inhibited thyroid Gs-protein and thyroid K+ channels. Considering the close relationship between G-protein and ion channels in the cardiac cell membrane, these different effects of Group Ia and Group Ib antiarrhythmic drugs on G-proteins and K+ channels are of interest. Further investigation is necessary to clarify the relationship between thyroid G-proteins and thyroid K+ channels.

Animals↗

PubMed1995

Cardiovascular system related peptides and hypothalamic neurons.

The hypothalamus is known to be an integrative site of cardiovascular, endocrine and autonomic functions. Our previous studies, using extracellular, intracellular and/or whole cell patch-clamp recordings in rat hypothalamic slice preparations, revealed that cardiovascular related peptides such as atrial natriuretic polypeptides (ANP), B-type polypeptides (BNP), endothelin (ET), angiotensin II (AII) and interleukin-1 beta (IL-1 beta) influence the hypothalamic neurons. ANP modulated the firing rates in the supraoptic nucleus (SON). BNP inhibited the SON neurons and these effects were mediated through cGMP and cGMP-dependent protein kinase. ET also inhibited approximately 60% of SON neurons. By using slice patch-clamp techniques, AII inhibited the transient outward potassium current in the SON neurons. IL-1 beta increased the firing rate and depolarized the membrane of the most SON neurons. A new type of transmitter, nitric oxide (NO), identified as an endothelial-derived relaxing factor (EDRF), modulated the glutaminergic inputs of the SON neurons. The results suggest that cardiovascular related peptides and NO modulate the neuronal activity of neurosecretory cells in the SON.

Angiotensin II↗

PubMed1994

Effects of centrally administered endothelin-3 on renal sympathetic nerve activity and renal blood flow in conscious rats.

Effects of intracerebroventricular (i.c.v.) administration of endothelin-3 (ET-3) on renal sympathetic nerve activity (RSNA) and renal blood flow (RBF), arterial blood pressure and heart rate were examined in conscious rats. Administration of ET-3 (1-50 pmol) through a chronically implanted cannula evoked an increase in arterial blood pressure and decreases in heart rate and RSNA, whereas RBF measured by Doppler flow probes did not change. Maximum changes in these responses occurred 10-15 min after i.c.v. administration of ET-3 and the responses returned to the control level after approximately 60 min. In sinoaortic denervated (SAD) rats, the decrease in RSNA induced by i.c.v. ET-3 was attenuated but still significantly persistent. During the experiments, we found that the injection of ET-3 (50-100 pmol) induced a barrel rotation, with an onset latency of 10-15 min. In those cases, prominent increases in arterial blood pressure and RSNA were observed, and these lasted for more than 60 min. The result shows that ET-3 can have centrally mediated effects on autonomic nerve activity as well as on cardiovascular function.

Animals↗

PubMed1993

Synaptic inputs from the stomach to tuberoinfundibular neurons in the paraventricular nucleus of the hypothalamus in rats.

In male rats anesthetized with urethane (600 mg/kg) and alpha-chloralose (60 mg/kg), extracellular recordings were made from tuberoinfundibular (TI) neurons in the paraventricular nucleus (PVN) identified by antidromic stimulation of the median eminence. Electrical stimulation of the gastric branches of the vagus nerve excited 26 (72%) of 36 TI neurons tested. I.v. (0.5-1 microgram/rat) or i.p. (5 micrograms/rat) administration of cholecystokinin (CCK-8) excited 10 (63%) of 16 TI neurons tested. The excitatory responses induced by CCK-8 were abolished by bilateral cervical vagotomy. These results suggest that TI neurons in the PVN receive excitatory inputs from gastric afferents via vagus nerves.

Animals↗

PubMed1993

The TSH-dependent potassium channel in a cloned rat thyroid cell line.

We found a TSH-dependent K+ channel in the membrane of a rat thyroid cell line (FRTL-5 cell). This K+ channel is activated by extracellular application of the thyroid stimulating hormone (TSH). Treatment of dibutyryladenosine cyclic monophosphate (Bt2 cAMP) also activated the TSH-dependent K+ channel. Intracellular application of protein kinase A activates this K+ channel without the presence of free Ca2+. These findings indicate that the thyroid K+ channel is activated through the TSH-cAMP-protein kinase A system. This is the first report of a polypeptide hormone activated K+ channel and it should be useful for examining the effects of this K+ channel on thyroid cell functions.

Amino Acid Sequence↗

PubMed1993

Lateral preoptic neurons inhibit thirst in the rat.

Kainic acid (KA) and muscimol were injected into the lateral preoptic area (LPO) of the rat to study their effects on drinking behavior. A low dose (5 ng) of KA, which stimulates neurons, decreased the amount of water intake induced by hypertonic saline (IP) and angiotensin II (SC). Injection of 2 ng muscimol, a potent GABAA receptor agonist that suppresses neurons, facilitated drinking responses induced by hypertonic saline, but did not affect angiotensin II-induced drinking. Rats injected with a high dose (150 ng) of KA, which destroys neurons, showed marked polydipsia accompanied by increased urination. One week after the KA lesion, drinking and urine output recovered to normal. During the polydipsia, a small volume of concentrated urine could be excreted if water intake was restricted. After recovery, excessive drinking responses followed water deprivation and hypertonic saline load. The rats normally drank water in response to angiotensin II and to polyethylene glycol solution. The results show that activation of LPO neurons inhibits water intake, and that suppression of LPO neurons facilitates osmotically induced water intake. Therefore, LPO neurons are probably involved in the inhibition of thirst.

Animals↗

PubMed1993

Vasopressin- and oxytocin-immunoreactive hypothalamic neurones of inbred polydipsic mice.

In the late 1950s the inbred polydipsic mice, STR/N, was discovered. The early studies indicated that the extreme polydipsia was not due to a lack of vasopressin but probably due to innate thirst of unknown origin. Because the recent investigation has revealed the presence of some functional abnormality in the brain of the STR/N mouse, we now investigated, using immunohistochemical techniques, distribution of vasopressin (AVP)- and oxytocin (OXT)-containing neurones in the hypothalamus of polydipsic strain of mouse and compared with that of the control. The pattern of distribution of AVP- and OXT-immunoreactive neurones in the paraventricular (PV), supraoptic (SO), and suprachiasmatic nuclei (SCN) of the STR/N polydipsic mouse was similar to that of the control, but the number of AVP-immunoreactive neurones was more numerous in the PVN and SON and less in the SCN in the polydipsic mouse than in the control. In addition, a discrete group of AVP- and OXT-containing neurones that was not clearly seen in the control was discovered in the STR/N. These results implicate that abnormal distribution in the brain AVP and OXT contribute to the mechanism responsible for the polydipsia shown by the strain STR/N.

Animals↗

PubMed1993

CCK-8 excites oxytocin-secreting neurons in the paraventricular nucleus in rats--possible involvement of noradrenergic pathway.

Systemic administration of CCK-8 increased plasma oxytocin (OXT) level in rats anesthetized with a mixture of urethane and alpha-chloralose. Extracellular recordings were made from magnocellular neurosecretory neurons in the paraventricular nucleus (PVN) of the hypothalamus in anesthetized rats to examine the effects of CCK-8 on the firing of PVN neurons. Thirteen out of 16 nonphasic neurons (putative OXT-secreting neurons) were excited by intravenous and/or intraperitoneal administration of CCK-8. By contrast, 8 out of 10 phasic cells, vasopressin(AVP)-secreting cells, were inhibited by systemic administration of CCK-8. Four out of five nonneurosecretory neurons in the PVN were excited by the administration of CCK-8. Moreover, microiontophoretically applied phentolamine blocked the excitatory responses induced by CCK-8 in nonphasic neurons. We measured extracellular noradrenaline (NA) level in the PVN, using in vivo microdialysis. Intravenous administration of CCK-8 induced NA release in the PVN. These results suggest that CCK-8 activates the excitatory afferent pathway to putative OXT-secreting neurons in the PVN which may, at least in part, be involved in the central noradrenergic projection.

Adrenergic Antagonists↗

PubMed1993

[Lung fibroblast growth-stimulating activity of serine protease].

We compared lung fibroblast growth-stimulating activity (FGA) of several serine proteases including thrombin in vitro, and examined the mechanism of FGA. FGA was measured by incorporation of 3H-thymidine into lung fibroblasts (IMR-90). The activities of the enzymes were measured by spectrofluorometric method with synthetic peptides specific for each enzyme, and these enzymes were added to the assay system for FGA at concentrations of 7 x 10(0)-7 x 10(5) unit/ml. Human thrombin, bovine trypsin and bovine alpha-chymotrypsin showed clear FGA, but that of alpha-chymotrypsin was lower than those of thrombin and trypsin. On the other hand, porcine pancreatic elastase and human neutrophil elastase did not show any FGA, and had a cytotoxic effect on fibroblasts. A specific low molecular-weight thrombin inhibitor, argatroban (MW. 562), inhibited not only the enzyme (peptidolytic) activity of thrombin, but also its FGA at the same concentration. These results suggest that serine proteases can be classified into at least two groups, showing FGA and cytotoxic activity, respectively, and that the FGA of the former group is mediated by their catalytic (enzymatic) action.

Animals↗