Biomedical subjects

I Wakabayashi

Publications and source records attributed to I Wakabayashi.

At least 55 records · Page 3Linked to original sources

PubMed1999

Ectopic corticotroph adenoma in the cavernous sinus: case report.

OBJECTIVE AND IMPORTANCE: Adrenocorticotropin (ACTH)-secreting pituitary adenomas causing Cushing's disease are often difficult to identify because of their variable locations and their small size. This report presents histological evidence of an ectopic ACTH-secreting adenoma located entirely within the cavernous sinus. CLINICAL PRESENTATION: A 62-year-old woman presented with central obesity, hypertension, and osteoporosis. Endocrinological evaluation suggested the presence of an ACTH-secreting pituitary adenoma; however, imaging studies, including dynamic magnetic resonance imaging, did not reveal any visible lesions in the pituitary gland. Bilateral cavernous sinus sampling demonstrated a large central/peripheral ACTH gradient, with a right/left ACTH gradient. The patient was treated as having pituitary-dependent Cushing's disease, until she died suddenly as a result of acute respiratory failure. INTERVENTION: In a postmortem histological examination, an ACTH-secreting adenoma was found in the right cavernous sinus, which was completely surrounded by dura mater and had no direct connection with the pituitary gland. CONCLUSION: Although they are rare, such adenomas located in the cavernous sinus should be recognized as one of the reasons for inaccurate cavernous sinus sampling and the failure of transsphenoidal surgery for patients with ACTH-dependent Cushing's syndrome.

ACTH Syndrome, Ectopic↗

PubMed1999

Inhibitory effects of baicalein and wogonin on lipopolysaccharide-induced nitric oxide production in macrophages.

In order to elucidate the mechanism of the antiinflammatory action of baicalein and wogonin, flavonoids from the root of Scutellaria baicalensis, the effects of these compounds were investigated on lipopolysaccharide-induced nitric oxide production in a macrophage-derived cell line, RAW 264.7. Baicalein (5-25 microM) and wogonin (5-50 microM) inhibited lipopolysaccharide-induced nitric oxide generation in a concentration-dependent manner. The inhibitory effect of these compounds was observed only when they were added at the start of cell incubation soon after the stimulation with lipopolysaccharide. Baicalein (25 microM) and wogonin (25 microM) also inhibited protein expression of inducible nitric oxide synthase. This inhibitory effect of wogonin was stronger than that of baicalein, which agrees with the result that wogonin showed stronger inhibition of nitric oxide production than baicalein. These results suggest that baicalein and wogonin attenuate lipopolysaccharide-stimulated nitric oxide synthase induction in macrophages and thus may help to explain the antiinflammatory action of these flavonoid compounds.

Animals↗

PubMed1999

Reduced growth hormone receptor messenger ribonucleic acid in an aged man with chronic malnutrition and growth hormone resistance.

A severely malnourished 87-yr-old man presented with hypoglycemia. Serum GH levels were elevated, and serum levels of insulin-like growth factor I (IGF-I), IGF-binding protein-3, and GH-binding protein were extremely reduced. The patient's GH was biologically active. Administration of GH for 4 consecutive days resulted in a slight increment in serum IGF-I levels, but no elevation of serum IGF-binding protein-3. The expression of GH receptor messenger ribonucleic acid in the liver was greatly reduced. An autopsy revealed a Rathke's cleft cyst confined to the sella turcica. Immunohistochemical studies for GH showed that there was nothing to suggest a tumor overproducing GH. In addition, TSH levels were elevated in the presence of normal thyroid hormone levels, and there was a cluster of cells showing strong immunohistochemical staining for the TSH beta-subunit in the pituitary. In this patient, the decreased expression of GH receptor messenger ribonucleic acid in the liver may have been responsible for the GH resistance, which was probably caused by malnutrition.

Aged↗

PubMed1999

Overexpression of fibroblast growth factor receptor 3 in a human thyroid carcinoma cell line results in overgrowth of the confluent cultures.

Recent reports indicate that a gain-of-function mutation in fibroblast growth factor receptor 3 (FGFR-3) inhibits cell growth in the cartilaginous growth plates. These results suggest that FGFR-3 may be the receptor transducing growth inhibitory signals. Using reverse transcription-PCR we examined seven papillary thyroid carcinomas to determine FGFR-3 expression. Six out of the seven papillary carcinomas expressed FGFR-3. To clarify the role of FGFR-3 in thyroid carcinoma, FGFR-3 was overexpressed in an established human papillary thyroid carcinoma cell line. High levels of FGFR-3 protein were identified in cells stably transfected with the vector containing FGFR-3 cDNA. The specific binding of 125I-FGF-2 of these cells was threefold higher than that of control cells. Growth rates of cells overexpressing FGFR-3 were similar to those of control cells. However, cells overexpressing FGFR-3 continued to grow beyond the density at which control cells stopped proliferating. These results suggest that FGFR-3 in thyroid carcinoma is not involved strongly in the cell proliferation mechanism but may contribute to the malignant extension of some of the carcinomas by modifying cell contact signaling.

Carcinoma, Papillary↗

PubMed1999

[Mechanism of inhibitory effects of ethanol on gallbladder contraction: differences in cases of histamine- and acetylcholine-induced contraction].

We investigated the effects of different concentrations of ethanol on contraction of gallbladder isolated from guinea pig. Ethanol at 25 mM significantly inhibited the contraction induced by histamine, but not those by KCl and acetylcholine. A higher concentration (100 mM) of ethanol inhibited both histamine-, acetylcholine- and KCl- induced contractions. The inhibitory effect of the lower concentration (25 mM) of ethanol was not observed in the presence of verapamil, an antagonist of L-type Ca2+ channel or staurosporine, a selective inhibitor of protein kinase C. Verapamil and staurosporine significantly inhibited both histamine- and acetylcholine-induced contractile responses: the inhibitory effect was more potent for the histamine contraction. Our recent study has demonstrated that contraction caused by protein kinase C activation is completely dependent on Ca2+ influx through the L-type Ca2+ channel in gallbladder smooth muscle of guinea pig. Therefore, the difference in 25 mM ethanol effect on histamine- and acetylcholine-induced contractions may be due to different degree of involvement of protein kinase C activation in the agonist-induced contraction. On the other hands, the higher concentration (100 mM) of ethanol inhibits the common pathway of contraction in gallbladder smooth muscle cells.

Acetylcholine↗

PubMed1999

Cadmium accumulation augments contraction and phosphoinositide hydrolysis of vascular smooth muscles.

Effects of cadmium accumulation in blood vessels on vasoconstriction and hydrolysis of phosphoinositides were investigated using aortas isolated from rats. The aortic strips were incubated with cadmium chloride (10 microM) for 24 hr and then washed out (cadmium accumulation). In the cadmium-accumulated aortas, contractile responses to KCl and 5-hydroxytryptamine were augmented compared to the control incubated with a vehicle. The degree of the augmentation by cadmium was higher in 5-hydroxytryptamine contraction than in KCl contraction. The level of 5-hydroxytryptamine-induced contraction relative to KCl-induced contraction (expressed as percent of maximum KCl contraction in each strip) was also significantly increased in the cadmium-accumulated aortas as compared to the control. Cadmium pretreatment augmented 5-hydroxytryptamine-stimulated inositol monophosphate accumulation, while there was no difference in the basal level of inositol monophosphate between the cadmium-accumulated aortas and the control. These results suggest that cadmium accumulation increases vasocontractility, in part because of the facilitation of phosphoinositide hydrolysis.

Animals↗

PubMed1998

Brain vasopressin is involved in stress-induced suppression of immune function in the rat.

The possibility that vasopressin (VP) is involved in stress-induced suppression of immune function was examined in rats. Intermittent electrical footshock for 60 min suppressed the proliferative response of splenic T cells to the mitogen concanavalin A as well as natural killer (NK) cytotoxicity, and the former change was partially, and the latter was completely, blocked by intracerebroventricular (i.c.v.) preadministration of a V1 receptor antagonist. The footshock-induced suppression of the T cell proliferative response was completely abolished by coadministration of a corticotropin-releasing hormone (CRH) receptor antagonist and the V1 receptor antagonist. The i.c.v. administration of VP suppressed the proliferative response of splenic T cells and NK cytotoxicity in an adrenal-independent manner. These effects were completely reversed by i.c.v. preadministration of the V1 receptor antagonist. These results suggest that brain VP, in conjunction with CRH, suppresses immune function through the V1 receptor in rats under stress.

Adrenalectomy↗

PubMed1998

The growth hormone secretagogue KP-102-induced stimulation of food intake is modified by fasting, restraint stress, and somatostatin in rats.

The effects of fasting, restraint stress, and intracerebroventricular (i.c.v.) injection of somatostatin on the growth hormone secretagogue, KP-102-induced stimulation of food intake were examined in rats. KP-102-induced stimulation of food intake was observed in freely-fed rats but not in 24-h starved rats. A 90 min period of restraint stress decreased food intake, and i.c.v. administration of KP-102 counteracted the suppressive effect of restraint on food intake. I.c.v. administration of somatostatin partially attenuated the KP-102-induced stimulation of food intake in freely-fed rats, while somatostatin itself did not change food intake. These results suggest that the stimulatory effect of KP-102 on feeding behavior is evident in freely-fed rats but not in starved rats, and that the effect of KP-102 is counteracted or attenuated by stress or somatostatin.

Animals↗

PubMed1998

Preferential inhibition by ethanol of phorbol ester-induced smooth muscle contraction of guinea pig gallbladder.

In order to investigate how ethanol inhibits the contractility of gallbladder smooth muscle, the effects of different ethanol concentrations were examined on gallbladder contractile responses to stimulants which act on the smooth muscle by different mechanisms. A low concentration (25 mM) of ethanol significantly inhibited the contractile response to phorbol-12,13-dibutyrate (PDBu), but not that to KCl. It also did not significantly affect contractile response to Ca2+ ionophore A23187 in the presence of verapamil or that to Ba2+ in a medium without Ca2+. On the other hand, a higher concentration (200 mM) of ethanol significantly inhibited the contractile responses to PDBu, KCl, Ca2+ ionophore A23187 and BaCl2. These results together with our recent finding that PDBu-induced contraction of guinea pig gallbladder is completely dependent on activation of the voltage-dependent Ca2+ channel suggest that low concentrations of ethanol selectively inhibit the signal transduction of gallbladder smooth muscle cells in the pathway from activation of protein kinase C to that of the voltage-dependent Ca2+ channel, while high concentrations of ethanol inhibit the intracellular common pathway (probably in the cytoskeletal apparatus).

Animals↗

PubMed1998

Genotype configuration in a case of primary gastric lymphoma with T-cell phenotype.

T-cell malignant lymphoma of the gastrointestinal tract is rare. The genotype of gastric T-cell lymphoma remains unclear. The aim of this study was to elucidate the pathogenesis of a case of primary gastric T-cell lymphoma by using cytogenetics and molecular biology. Gastric biopsy specimens and lymphoma cells in the ascites were examined by immunocytology, cytogenetic analysis, and Southern blot analysis. The histological diagnosis of the gastric lymphoma was diffuse large cell type. T-cell markers were positive in immunocytochemistry of the gastric lymphoma cells and in FACS analysis of lymphoma cells in the ascites. All lymphoma cells in the ascites had complex abnormal karyotypes containing t(8;14)(q24;q32). Southern blot analysis revealed rearrangement of the IgH and C-MYC genes of the lymphoma cells in both the stomach and the ascites, but no comigration of the C-MYC with the JH locus could be detected. The TCR-beta and -gamma genes were in their germ-line configurations. In this patient, although the phenotype was T-cell lymphoma, the karyotype t(8;14)(q24;q32) and genotype had the characteristics of B-cell lymphoma. The unique B-cell genotype configuration and the C-MYC activation suggested that the cellular origin of this rare case of malignant lymphoma with a T-cell phenotype was quite immature lymphocytes.

Adult↗

PubMed1998

Growth factors increase pericellular proteoglycans independently of their mitogenic effects on A10 rat vascular smooth muscle cells.

Proliferation of vascular smooth muscle cells with the accumulation of proteoglycans in the extracellular matrix is one of the significant changes found in atherosclerotic lesions. In order to clarify the relationship between pericellular proteoglycan and cell growth, we established a simple method for quantitatively estimating the amount of pericellular proteoglycans and investigated the effects of various growth factors on the synthesis of pericellular proteoglycans by cultured A10 rat smooth muscle cells. Analysis of trypsin accessible [35SO4]-labeled material in the pericellular area of the A10 cell culture by Q-sepharose anion-exchange chromatography showed two peaks. One peak, eluted at 0.55 M NaCl, disappeared after treatment with 2 mU/ml of heparitinase, indicating that heparan sulfates (HS) were present. The other peak, which eluted at 0.65 M NaCl, disappeared with 20 mU/ml of chondroitinase ABC, indicating the presence of chondroitin sulfates and dermatan sulfates (CS/DS). We estimated the effects of several growth factors on the synthesis of the pericellular proteoglycans by measuring heparitinase- and chondroitinase-ABC-sensitive radioactivities. Although PDGF-AB significantly stimulated cell proliferation and the synthesis of pericellular CS/DS, its dose-dependent effect on the cell growth did not coincide with that on the proteoglycan synthesis. IGF-I (1 nM) increased pericellular CS/DS but not the cell number, while basic FGF (1 nM) and EGF (1 nM) increased the cell number but not pericellular CS/DS. All the growth factors we examined had no effect on the synthesis of pericellular HS. These results indicate that growth factors increase pericellular proteoglycans independently of their mitogenic effects.

Animals↗

PubMed1998

Serum sialic acid and ankle versus brachial arterial-pressure ratio in NIDDM.

Serum sialic acid is related to mortality from cardiovascular disease and is increased in patients with diabetic microangiopathies. The purpose of this study was to examine whether serum sialic acid is associated with ischemic disease of the lower extremities, using the ankle versus brachial arterial-pressure ratio. The subjects were NIDDM patients attending diabetic clinics. They received a questionnaire on smoking and duration of diabetes, and physical examinations including measurement of blood pressure of upper and lower extremities. Fasting blood was taken for measurement of sialic acid, total and HDL cholesterol, and HbA1c. Serum sialic acid was significantly correlated with ankle versus brachial arterial-pressure ratio (r = -0.32) and HbA1c (r=0.45). The correlation with ankle versus brachial arterial-pressure ratio was evident in the patients with low ankle versus brachial arterial-pressure ratios (r = -0.66), but was not significant in those with normal ankle versus brachial arterial-pressure ratios (r=0.16). The correlation with HbA1c was significant independently of ankle versus brachial arterial-pressure ratios. Mean serum sialic acid was higher in patients with very low ankle versus brachial arterial-pressure ratios (< 0.9) than in those with normal ankle versus brachial arterial-pressure ratios (> or = 1.0) or slightly low ankle versus brachial arterial-pressure ratios (0.9 approximately 1.0). These results suggest that serum sialic acid reflects the status of blood glucose control and the progression of ischemic disease of the lower extremities in NIDDM patients.

Ankle↗

PubMed1998

Fibroblast growth factor-2 free from extracellular matrix is increased in papillary thyroid carcinomas and Graves' thyroids.

Fibroblast growth factor (FGF)-2 is stored in the extracellular matrix (ECM). We hypothesized that FGF-2 is mobilized from the ECM and binds to receptors on the surface of FGF-2 responsive cells during thyroid enlargement. To test this hypothesis, we estimated levels of FGF-2 free from ECM in thyroids by comparing the efficiency of two methods for FGF-2 extraction (low salt and high salt). Because the high salt concentration (more than 1.5 M NaCl) is necessary to release FGF-2 from the normal ECM, FGF-2 extracted by low salt is indicative of ECM-free FGF-2. Human papillary thyroid carcinomas, normal part thyroid, and Graves' thyroid tissues were homogenized separately in an extraction buffer containing either 0 M NaCl (low salt) or 2.0 M NaCl (high salt), and the concentration of FGF-2 in the extracts was measured by enzyme-linked immunosorbent assay (ELISA). The yields of low and high salt extracts of immunoreactive (ir)FGF-2 from papillary carcinomas (low salt: 40.0 +/- 7.5, high salt: 233 +/- 53 ng/g tissue, mean +/- SE) were significantly higher than those of normal thyroid tissues extracted by the corresponding salt concentration (low salt: 14.6 +/- 1.8, high salt: 123 +/- 12 ng/g tissue). On the other hand, the extractable irFGF-2 from Graves' thyroid tissues (low salt: 25.2 +/- 2.5, high salt: 135 +/- 24 ng/g tissue) were not significantly different from that of normal thyroid tissues. However, the ratio of the extractable irFGF from carcinomas and Graves' thyroids by low salt to that by high salt (0 M/2 M ratio = 0.206 +/- 0.051, 0.209 +/- 0.025) were significantly higher than that of normal thyroids (0.120 +/- 0.014) (p < 0.05). These results suggest that intratissue ECM-free FGF-2 is increased in papillary thyroid carcinomas and Graves' thyroid tissues, and therefore a greater amount of FGF-2 may be available for stimulation of FGF-2 responsive cells.

Blotting, Western↗

PubMed1998

Growth hormone-dependent regulation of pituitary GH secretagogue receptor (GHS-R) mRNA levels in the spontaneous dwarf Rat.

Growth hormone secretagogues (GHSs) are synthetic peptidyl and nonpeptidyl compounds that are believed to stimulate the release of GH by a direct effect on the pituitary somatotrope and by stimulation of growth hormone-releasing hormone (GHRH) release and the suppression of somatostatin (SRIH) tone. Recently, the receptor for these pharmacologic agents was cloned and its expression localized to the pituitary and hypothalamus. The elucidation of an unique GHS receptor (GHS-R) suggests there is a yet to be identified endogenous ligand which could exert an important role in regulation of GH secretion. It is clearly established that GH acts to regulate its own production by feeding back at the level of the hypothalamus to downregulate GHRH and upregulate SRIH synthesis and by induction of IGF-I, which acts at the pituitary to block somatotrope responsiveness to GHRH. If the endogenous GHS/GHS-R signaling system is important in regulating GH release, it might be reasoned that changes in circulating GH concentrations would also directly or indirectly (via generation of IGF-I) modify GHS-R production. To test this hypothesis we used RT-PCR to examined pituitary and hypothalamic GHS-R mRNA levels in the spontaneous dwarf rat (SDR), an animal model characterized by the absence of GH due to a point mutation in the GH gene. In the absence of GH feedback regulation, SDR pituitary GHS-R mRNA levels were 385 +/- 61% greater (p < 0.01) than those observed in normal controls while SDR hypothalamic GHS-R mRNA levels were not significantly different from those in normal rats. Three-day subcutaneous infusion of rat GH by osmotic pump reduced SDR pituitary GHS-R mRNA levels to 55 +/- 9% of vehicle-treated controls (p < 0.05) but did not significantly alter hypothalamic GHS-R mRNA levels. To test if the changes in GHS-R mRNA levels observed following GH treatment were due to elevation of circulating IGF-I concentrations, SDRs were infused with recombinant human IGF-I. Replacement of IGF-I did not significantly alter either pituitary or hypothalamic GHS-R mRNA levels, indicating that GH acts independent of circulating IGF-I to regulate pituitary GHS-R expression in the SDR model.

Animals↗

PubMed1998

Interleukin-1beta administered intracerebroventricularly stimulates the release of noradrenaline in the hypothalamic paraventricular nucleus via prostaglandin in the rat.

We evaluated the effect of intracerebroventricular (i.c.v.) administration of interleukin (IL)-1beta on the rectal temperature and the release of noradrenaline (NA) in the hypothalamic paraventricular nucleus (PVN) of the rat. IL-1beta increased rectal temperature at doses ranging from 300 pg to 300 ng, whereas it, at doses ranging from 3 ng to 300 ng, significantly stimulated the release of NA in the PVN measured by intracerebral microdialysis. The stimulatory effect of IL-1beta on the release of NA was blocked by the subcutaneous injection of indomethacin. These findings suggest that IL-1beta stimulates the release of NA in the PVN via prostaglandin, and that the release of NA in the PVN is not necessarily related to the increase in body temperature.

Animals↗

PubMed1998

Growth hormone inhibits its own secretion by acting on the hypothalamus through its receptors on neuropeptide Y neurons in the arcuate nucleus and somatostatin neurons in the periventricular nucleus.

GH secretion is regulated by hypothalamic somatostatin and GH-releasing factor. It has been postulated that GH feeds back on the hypothalamus and regulates its own secretion. We focused our attention on the action of GH in the hypothalamus in relation to GH secretion. Adult male rats were used throughout the studies, and the observation was made in conscious rats. Systemic administration of human GH induced c-fos gene expression, a marker of neuronal activity, in the hypothalamic arcuate nucleus (ARC) and the periventricular nucleus (PeV) in hypophysectomized male rats. The major cells in which c-fos gene expression was induced were neuropeptide Y (NPY) neurons in the ARC and somatostatin neurons in the PeV. GH receptor mRNA was demonstrated to be present in these neurons by in situ hybridization. The injection of a small dose of rat GH into the ARC or PeV inhibited GH secretion, whereas microinjection of IGF-I into these nuclei did not. Intracerebroventricular injection of NPY suppressed GH secretion, and this effect was abolished by anterolateral deafferentation of the medial basal hypothalamus (MBH), a procedure which disrupts the somatostatinergic input to the MBH. Taken together, these findings suggest that GH acts on NPY neurons in the ARC and somatostatin neurons in the PeV through GH receptor, and the activation of these neurons augments somatostatin release and inhibits GH secretion.

Animals↗

PubMed1998

Age-related change in relationship between body-mass index, serum sialic acid, and atherogenic risk factors.

In order to clarify the significance of obesity in atherosclerotic risk at different ages, the relationship between the body-mass index, serum sialic acid concentration, and various atherosclerotic risk factors were investigated for healthy subjects in three different age groups, 35-39, 40-49 and 50-59 years old. The body-mass index correlated significantly with mean arterial blood pressure, fasting blood sugar, serum triglycerides, atherogenic index and serum uric acid in all age groups. The magnitudes of the association of body-mass index with mean arterial blood pressure, fasting blood sugar and serum triglycerides decreased with age, while those of the association with atherogenic index and serum uric acid were not different among the three age groups. Body-mass index did not show significant correlation with white blood cell count, platelet count or smoking in any of the age groups. Simple and multiple regression analyses showed that body-mass index was significantly correlated with serum sialic acid in the 35-39-year-old group, but not in the other two groups. Neither the percentage of obese subjects (body-mass index > 26.4) nor the mean values of body-mass index were different among the three groups. These results suggest that for younger people, the body-mass index is related more closely with some atherosclerotic risk factors (e.g. blood pressure, blood sugar and serum triglycerides), and obesity may be possibly more involved in the progression of atherosclerosis, compared to more elderly people.

Adult↗

PubMed1998

Ethanol inhibits intra- and extracellular Ca(2+)-dependent contraction of rat aorta by different mechanisms.

The mechanism of the inhibitory action of ethanol on vasoconstriction was studied by examining ethanol effects on vascular responses to different vasoconstrictive stimulants using isolated rat aorta. Ethanol pretreatment of aortic strips at 200 and 400 mM significantly inhibited contractile responses to KCl and 5-hydroxytryptamine in the standard medium. This inhibitory effect on vasoconstriction was observed whether or not the endothelium was present. Pretreatment with ethanol (400 mM) caused significant decrease of 45Ca2+ uptake induced by KCl when compared to the control. This pretreatment also significantly inhibited the contractile response to 5-hydroxytryptamine in the medium without Ca2+, decreased 5-hydroxytryptamine-stimulated inositol monophosphate accumulation, and significantly inhibited a transient contraction induced by 20 mM caffeine. Ethanol (400 mM) inhibited phorbol 12, 13-dibutyrate (PDBu)-induced contraction when Ca2+ was present in medium, but not when it was absent. These results suggest that ethanol acts on different sites of the signal transduction pathway of rat aortic smooth muscle, causing inhibition of transmembraneous Ca2+ influx through voltage-dependent Ca2+ channels, phosphoinositide hydrolysis and Ca(2+)-induced Ca2+ release. However, the cytoskeletal contractile apparatus may remain intact after ethanol treatment.

Animals↗