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RIE IDE, HIROSHI MAEGAWA, ATSUNORI KASHIWAGI, RYUICHI KIKKAWA, YUKIO S ...
1995 Volume 42 Issue 1 Pages
1-8
Published: 1995
Released on J-STAGE: November 21, 2006
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The mechanisms for the insulin resistance induced by hyperglycemia were investigated by studying the
in vitro effects of a high glucose concentration on insulin signaling with Rat 1 fibroblasts exressing human insulin receptors (HIRc). Incubation of HIRc cells for 4 days in 27mM D-glucose led to impaired insulin-stimulation of both α-aminoisobutyric acid uptake (AIB) and phosphorylation of pp185 and receptor β-subunits
in vivo. In vitro autophosphorylation and tyrosine kinase activities toward poly Glu
80 Tyr
20 of insulin receptors from cells exposed to high glucose media (HG) were also impaired (46-48% of control), although the binding of insulin to HG cells was unchanged. One possible explanation for these high glucose effects is that they are mediated by the activation of protein kinase C (PKC). However, a 4-day-high glucose culture had no effect on cytosolic and membrane PKC activities or on phorbol dibutyrate binding to whole cells. This is in accordance with the orthophosphate labeling study, in which basal autophosphorylation activity in HG cells did not increase, suggesting that phosphorylation of serine and threonine residues in the basal state might not increase in HG cells. These results indicate that in cells exposed to high glucose, desensitization of insulin receptors was induced via several intracellular events, but might not be due to persistent activation of PKC in HIRc cells.
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YUJI TANAKA, HIROOMI FUNAHASHI, TSUNEO IMAI, JYUNICHI TOBINAGA, HIROSH ...
1995 Volume 42 Issue 1 Pages
9-14
Published: 1995
Released on J-STAGE: November 21, 2006
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Heterotransplantation of human parathyroid tissues into nude mice was performed to investigate the characteristics of grafted tissues. Grafts prepared from hyperplasia, adenoma and normal glands which were resected at operation were implanted in the gluteus muscle of the recipient mice (female, KSNnu/nu strain). Graft function was evaluated by measuring human intact PTH concentrations in sera of the mice. Serum PTH concentrations 12 weeks after transplantation were correlated with the tissue volume in the mice which received one, two, four or eight pieces of 1mm
3 hyperplastic tissues. Changes in graft function were examined in the mice which received four grafts prepared from hyperplasia, adenoma or normal glands. Transplantation of parathyroid tissues resulted in an increase in PTH concentrations for 4 weeks, reaching a plateau thereafter. The level remained unchanged for 8 weeks. Serum PTH levels in the mice with grafts prepared from hyperplasia or adenoma were significantly higher than in those with grafts from normal glands, though without a significant difference between the mice with grafts from adenoma and from hyperplasia. Serum calcium levels were similar in all three groups. We also observed the response of grafted parathyroid tissue to a low calcium level in sera: there was higher PTH secretion four weeks after the administration of the low calcium diet. The success of heterotransplantation was histologically proven by the presence of grafts which were not atrophic in the muscle 12 weeks after transplantation. Nucleoli were found more frequently, and nuclear pleomorphism was observed in the cells of heterografts.
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Comparison of Platelets and Mononuclear Leucocytes
HIROMICHI SUZUKI, HIROTAKA SHIBATA, MAROHITO MURAKAMI, ATSUHISA SATO, ...
1995 Volume 42 Issue 1 Pages
15-22
Published: 1995
Released on J-STAGE: November 21, 2006
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The objective of the present study was to quantify the expression of angiotensin II type 1 (AT1) receptor transcripts in human blood cells-platelets and mononuclear leucocytes-from 10 normal healthy volunteers during the alterations in the renin-angiotensin system. A quantitative assay employing reverse transcription-polymerase chain reaction (RT-PCR) was utilized. Oral administration of furosemide, 40mg for 2 days, under mild salt restriction (50mEq NaCl/day) for 6 days stimulated the rennin-angiotensin system resulting in significant increases in plasma renin activity (PRA) (1.84±0.12
vs. 1.05± 0.17ng/
l/s;
P<0.01), plasma angiotensin II concentration, and plasma aldosterone concentration (PAC). The ratio of AT1 receptor mRNA to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA expression in mononuclear leucocytes was significantly (
P<0.05) increased from the basal level (0.49±0.05
vs. 0.29±0.03) (
P<0.01), while in platelets these changes were opposite (0.11±0.05
vs. 0.25±0.05) (
P<0.01). Compared to these significant changes, salt loading (200mEq NaCl/day) for 6 days decreased PRA(0.49±0.10
vs. 1.05±0.17ng/
l/s;
P<0.01) and induced the opposite changes in the ratio of AT1 receptor/GAPDH mRNA. These data suggest that AT1 receptors in human blood cells may be of two different types-platelets and mononuclear leucocytes.
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UCHE PETER ISICHEI, ISAO MORIMOTO, SONTASH CHANDRA DAS, JOHN ONYEANI E ...
1995 Volume 42 Issue 1 Pages
23-29
Published: 1995
Released on J-STAGE: November 21, 2006
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This study is an endemic goiter survey of 3476 school children in 13 Local Government Councils (LGCs) and 1004 subjects in a whole community of one LGC, Plateau State, Northern Nigeria, to determine the prevalence of goiter as well as to identify some of the etiological agents involved. Results of the survey showed that the disease is highly endemic in the area with prevalence varying in places from 1 to 23% of these subjects. Females showed a markedly higher prevalence of goiter. Analysis of 729 urine samples indicated that iodine excretion ranged from 3.5 to 15.3μg/d
l (32-154μg/g creatinine) and was similar to that in iodine deficient areas in the world, but no relation was observed between the prevalence of goiter and urinary iodine. Urinary thiocyanate levels were less than 0.5mg/d
l, suggesting that the role of thiocyanate as a goitrogen is not important in the region. Thyroid hormone parameters in village subjects with goiter were similar to those in goiter endemia except serum thyroxine (T
4). An interesting result found in village subjects was very high serum thyroxine binding globulin, which leads to an increase in serum T
4. This study indicated that Northern Nigeria is an area of endemic goiter. Although some areas in Plateau State are iodine deficient zones, we could not conclude that the etiology of endemic goiter in this area is associated with iodine deficiency. There may be an interplay of multiple factors of etiological importance.
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MASAZUMI NAGAI, TAKAYUKI NEMOTO, TOMOYUKI MASUDA, MINORU OTA
1995 Volume 42 Issue 1 Pages
31-38
Published: 1995
Released on J-STAGE: November 21, 2006
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In this study, we examine the effect of testosterone on the steady-state concentration of androgen receptor (AR) mRNA of mouse submandibular gland. Northern blot analysis showed the expression of an AR-specific 10-kb transcript in the submandibular glands of both sexes. Quantitative analysis was done by means of reverse transcription-polymerase chain reaction (RT-PCR) with a non-radioactive label of digoxigenin. The RT-PCR demonstrated that the steady-state of AR mRNA concentration was less in males than in females. Moreover, AR mRNA increased in the castrated male mice, while the administration of testosterone reduced the AR mRNA in female mice. In conclusion, the amount of AR mRNA in mouse submandibular gland is reduced by androgen.
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SHINSUKE HIRAMATSU, YASUHIRO SAKO, KAZUO MIMURA, YASUHIRO ONO, KENICHI ...
1995 Volume 42 Issue 1 Pages
39-42
Published: 1995
Released on J-STAGE: November 21, 2006
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By means of the euglycemic three step hyperinsulinemic clamp technique, suppression of endogenous C-peptide secretion by exogenous insulin infusion was evaluated in patients with insulinoma (n=8) and healthy controls (n=20). Euglycemic hyperinsulinemic clamp studies were performed with an artificial pancreas (STG-22 NIKKISO, Tokyo, Japan). Insulin (Actrapid human insulin) was infused at the rate of 1.12, 3, and 10mU/kg/min. Plasma glucose levels were clamped at 80mg/d
l, and high insulin levels were maintained in all subjects (833±78μU/m
l at the rate of 10mU/kg/min insulin infusion). During the clamp studies, plasma C-peptide levels in normal subjects declined from 2.0±0.2 to 0.9±0.2ng/m
l, indicating suppression of endogenous insulin secretion by exogenous insulin infusion. In patients with insulinoma, plasma C-peptide levels were 3.1±1.6ng/m
l in the basal state, and were not suppressed even during exogenous hyperinsulinemia. We concluded that the feedback inhibition of insulin secretion by exogenous insulin infusion is attenuated in patients with insulinoma, and that the hyperinsulinemic clamp technique may be a useful method for the diagnosis of insulinoma.
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KUNIHIKO HANEW, ATSUSHI UTSUMI, AKIRA SUGAWARA, AKI TANAKA, HIROSHI FU ...
1995 Volume 42 Issue 1 Pages
43-47
Published: 1995
Released on J-STAGE: November 21, 2006
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The mechanism of aberrant GH responses to TRH was indirectly evaluated in 7 patients with primary hypothyroidism. All patients showed GH response to TRH. When TRH was administered together with GHRH, the plasma GH response was much greater than after a single administration of TRH or GHRH (TRH+GHRH
vs. TRH or GHRH: max. Δ GH, 16.4±3.2
vs. 5.4±1.3 or 6.0±0.8μg/L; AUC, 1282.7±234.7
vs. 384.0±95.0 or 441.8±66.2, both
P<0.01). The combined administration of TRH and GHRH caused an additive, but not a synergistic, GH response. In contrast, 8 normal subjects showed neither any plasma GH response to TRH nor enhancement by TRH of GHRH-induced GH response following combined administration. It is concluded that the sites of action of TRH seemed to be different from GHRH in patients with primary hypothyroidism.
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NORIYUKI KOIBUCHI, SADAO YAMAOKA, MITSUO SUZUKI
1995 Volume 42 Issue 1 Pages
49-55
Published: 1995
Released on J-STAGE: November 21, 2006
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In order to detect the localization of c-
erbAα2 mRNA in the hypothalamus and its surrounding structures,
in situ hybridization histochemistry was performed in the adult male rat. Sections through the hypothalamus were hybridized with a [
3H]-labeled RNA probe complementary to c-
erbAα2 mRNA and then coated with photographic emulsion. Autoradiograms were then developed and localization of the hybridization signal was detected under a light microscope. Hybridization signal was detected throughout the hypothalamic and extrahypothalamic structures such as the paraventricular hypothalamic nucleus (PVN), ventromedial nucleus (VMN), arcuate nucleus (Arc), amygdala (Am), habenula (Hb), paraventricular thalamic nucleus (PVT) and hippocampus (Hipp). No hybridization signal was detected in the section which was hybridized with the sense probe. These results not only confirm previous findings in the PVN, Hb, PVT and Hipp, but also extend the finding to the VMN, Arc and Am, in which cells expressing c-
erbAα2 primary transcript were concentrated. These new findings may provide an important aid to the understanding of the roles of thyroid hormone in the function of the central nervous system.
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AKITO MIYAUCHI, YUTAKA OSUGA, YUJI TAKETANI
1995 Volume 42 Issue 1 Pages
57-62
Published: 1995
Released on J-STAGE: November 21, 2006
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In a primary human endometrial cell culture, the addition of progesterone resulted in an approximately 2-fold increase in the amount of tissue-type plasminogen activator (t-PA) released into the culture media, with the minimal effective dose being 10
-7M. In contrast, progesterone significantly reduced the release of urokinase-type PA (u-PA). Endometrial cells are known to release a major PA inhibitor, PAI-1. Progesterone stimulated the release of PAI-1. These observed effects of progesterone seem to be mediated through the progestin receptor in that R5020, a specific ligand for progestin receptor, mimicked the effects of progesterone, and RU486, an antagonist of progesterone, completely eliminated the effects of progesterone. It is notable that estradiol, when added alone or in combination with progesterone, caused no discernible effect on the release of PAs and PAI-1. These results suggest that progesterone is a key hormone in regulating the PA/plasmin system in the human endometrium, thereby playing a pivotal role in implantation and ensuing embryonal development.
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MEGUMI FURUKAWA, YUZURU ETO, ITARU KOJIMA
1995 Volume 42 Issue 1 Pages
63-68
Published: 1995
Released on J-STAGE: November 21, 2006
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Expression of activin A in fetal rat pancreas was studied immunohistochemically by using anti-activin A antibody. On embryonic day 12 (E12), cells in cap-like pancreatic anlage were stained with anti-activin A antibody. In these sections, no immunoreactive insulin or glucagon was observed. On E13.5, cells containing immunoreactive activin A were observed in pancreatic anlage. These cells were also stained by both anti-glucagon and anti-insulin antibodies. On E15, a cluster of cells could be recognized as a primitive islet. In the primitive islet, cells containing immunoreactive activin A were observed. Activin-positive cells were located mainly in the mantle of the primitive islet but some were located in the core of the primitive islet. These activin-positive cells also expressed glucagon. Among them, cells also containing insulin were observed. In. addition to activin-positive cells, cells containig only insulin were detected in the core of the primitive islet. These results indicate that immunoreactive activin A is expressed in fetal pancreas. The expression of activin A is an early event during the development of pancreatic endocrine cells.
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MARIKO SHIROTA, MASAMICHI KUROHMARU, YOSHIHIRO HAYASHI, KINJI SHIROTA, ...
1995 Volume 42 Issue 1 Pages
69-76
Published: 1995
Released on J-STAGE: November 21, 2006
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Biotinylated riboprobe that specifically hybridized with messenger RNAs (mRNAs) encoding the long form of prolactin receptor (PRLR
L) was transcribed from 269 by Hind III and Xho I fragment of the cytoplasmic domain of PRLR
L complementary DNA (cDNA). The probe was used for
in situ hybridization to identify tissue localization of PRLR
L mRNA in the mammary gland, liver, ovaries and kidneys from lactating rats at 24-36h after delivery. Histochemical detection of signals by means of horseradish peroxidase (HRP)-labeled streptavidin revealed that the PRLR
L gene was expressed on the alveolar epithelial cells and mammary ductal epithelium in the mammary gland, and hepatocytes in the liver. In the ovary, the PRLR
L gene was expressed on the luteal cells in the newly formed corpus luteum, granulosa cells and theca cells of follicles at various stages of development, hypertrophied theca cells in the atretic follicle, and secondary interstitial cells, but no signal was observed in the kidney. Biotinylated sense RNA probe did not detect any signals in any of the tissues examined.
In situ hybridization with nonradiolabeled probe provided the identification of PRLR
L mRNA in the fine tissues, such as follicular epithelium in the ovary, and showed the morphology of individual cells expressing the PRLR
L gene. In particular, the diversity of signal intensity in the same mammary gland with different appearances suggested the existence of a local mechanism controlling PRLR
L gene expression.
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SHIGENORI NAKAMURA, YUKIE SAIO, TAKESHI SHIMADA, IKUO MATSUI
1995 Volume 42 Issue 1 Pages
77-81
Published: 1995
Released on J-STAGE: November 21, 2006
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We report the case of a 41-year-old female with untreated Graves' disease who developed transient hypothyroidism. The hypothyroid state was thought to be caused by silent thyroiditis, based on findings of a non-tender thyroid gland, suppressed thyroidal radioactive iodine uptake, normal white blood cell count and normal erythrocyte sedimentation rate, and ultrasonogram results. Silent thyroiditis may play a role in the development of Graves' hyperthyroidism. Results for TSH-binding inhibitor immunoglobulins (TBII), thyroid-stimulating antibodies (TSAb), anti-thyroglobulin antibodies (TgAb) and anti-thyroid peroxidase antibodies (TPOAb) were positive before the development of hypothyroidism. Their levels were decreased during and after the hypothyroid phase. These results suggest that the same or similar mechanism(s) were involved in the production of these different antibodies during the course of her illness.
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TOSHINARI TAKAMURA, KENSOU OHSAWA, YASUYUKI NISHIMURA, SHOICHI YAMAGIS ...
1995 Volume 42 Issue 1 Pages
83-88
Published: 1995
Released on J-STAGE: November 21, 2006
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A case of ACTH deficiency and partial GH deficiency associated with neurohypophyseal ectopy is described. A 42-year-old woman of short stature was admitted for hypoglycemic coma. The patient had hypocortisolemia, an increase in urinary 17-OHCS after consecutive injections of ACTH-Z, and a low plasma ACTH level which showed no response to corticotropin-releasing factor. This indicated the presence of ACTH deficiency. The plasma GH level showed a blunted response to insulininduced hypoglycemia, but its response to GRF was preserved. Other hypothalamo-pituitary axes were intact. T1-weighted magnetic resonance imaging demonstrated ectopic neurohypophyseal tissue and a tiny anterior pituitary remnant. ACTH deficiency and partial GH deficiency might have developed as a consequence of pituitary stalk injury and inadequate regeneration of the anterior lobe.
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KEIICHI KAWAMOTO, TOHRU UOZUMI, KAZUNORI ARITA, AKIHIKO TAKECHI, HITOS ...
1995 Volume 42 Issue 1 Pages
89-93
Published: 1995
Released on J-STAGE: November 21, 2006
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To detect growth hormone-releasing hormone (GHRH) secreted by monodispersed human GH-producing pituitary adenoma cells, the cell immunoblot assay was performed. GHRH-secreting cells were observed in 3 cases of GH-producing pituitary adenomas. The incidence of GHRH-secreting cells in the total cell populations was 0.24-3.42%. By contrast, no GHRH-secreting cells were observed in 2 cases of clinically nonfunctioning pituitary adenomas. The findings obtained by immunohistochemical studies for adenohypophysial hormones and for nuclear antigens of proliferative activity revealed that the incidence of GHRH-secreting cells is more related to the frequency of GH cells than to the proliferative activity in GH-producing pituitary adenomas.
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REIKO DEMURA, SAEKO TAJIMA, TOMOHARU SUZUKI, RIE YAJIMA, EMI ODAGIRI, ...
1995 Volume 42 Issue 1 Pages
95-100
Published: 1995
Released on J-STAGE: November 21, 2006
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Inhibin and activin are known to be involved in the pituitary hormone secretion as well as proliferation of the pituitary. We studied the expression of inhibin α, and β
A subunit and activin type II receptor (ACTR 2) mRNAs in human pituitary adenomas to determine the significance of inhibin and activin in pituitary hormone secretion. Tumor tissues were homogenized immediately after resection in guanidinium thiocyanate to extract total RNA. PCR was performed with reversely transcripted cDNA and respective amplification primers. DNA bands obtained for inhibin α, β
A and ACTR 2 by agarose gel-electrophoresis were 367, 285, and 389 bp, respectively. Messenger RNAs for inhibin β
A were demonstrated in all of the pituitary tissues studied, namely in 3 GH, 2 ACTH, 6 PRL and 1 FSH producing adenomas and 17 non-functioning adenomas. Inhibin α mRNAs were detected in 10 of 12 functioning adenomas and 15 of 17 non-functioning adenomas. ACTR 2 mRNAs were found in 11 out of 17 nonfunctioning adenomas, but only found in 3 out of 12 functioning adenomas. These results suggested local production of activin, a homodimer of β-subunits, and inhibin, a heterodimer of α and β subunits, in most of the pituitary adenomas regardless of their hormone secretion. On the other hand, a significantly higher incidence of ACTR 2 in non-functioning adenomas than in functioning adenomas suggested that activin had its main site of action in non-functioning adenomas, which could be potential gonadotropinomas.
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Effect of Subcutaneous Injection of Human Recombinant Insulin-like Growth Factor-I
YOSHITAKA KAJIMOTO, RYUZO KAWAMORI, YOSHIO FUJITANI, MICHIHIKO KISHIMO ...
1995 Volume 42 Issue 1 Pages
101-105
Published: 1995
Released on J-STAGE: November 21, 2006
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We saw a 57-yr-old female non-insulin dependent diabetes mellitus (NIDDM) patient with antiinsulin antibody, in whom insulin-like growth factor- I (IGF-I) was shown to be effective as a blood glucose-lowering agent. Due to the presence of the antibody, the patient suffered from postprandial hyperglycemia and frequent hypoglycemia, which were uncontrollable even by multiple insulin injection therapy. In contrast to insulin injection (0.24IU/kg body wt) which showed a delayed glucoselowering effect, subcutaneous injection of recombinant human IGF-I (0.05-0.1mg/kg body wt) caused a quick fall in plasma glucose levels. Prolongation of the glucose-lowering effect of “rapid-acting” insulin frequently caused subsequent hypoglycemia in this patient, but the effect of IGF-I seemed to have disappeared within the first three hours.
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FUMI SHIMA, YOSHIHIKO ISHIDA, KAZUHIKO HOTTA, HARUHIKO HAGINO, TOSHIKI ...
1995 Volume 42 Issue 1 Pages
107-113
Published: 1995
Released on J-STAGE: November 21, 2006
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The tissue sensitivity to insulin was evaluated using the hyperinsulinemic euglycemic clamp technique in a 44-year old male with Werner's syndrome associated with diabetes mellitus. In addition, the autophosphorylation of insulin receptors and the number of autophosphorylated insulin receptors were measured in his erythrocytes by a new enzyme-linked immunosorbent assay. He had an increased serum insulin level (30.5μU/m
l) in addition to hyperglycemia (226mg/d
l), suggesting that he had insulin-resistant diabetes mellitus. A clamp study revealed that his insulin-stimulated glucose disposal rate (2.80mg/kg/min) was comparable to that in noninsulin-dependent diabetes mellitus (4.14±1.94 (SD)mg/kg/min, n=23). The number of autophosphorylated insulin receptors per 300μ
l of erythrocytes was also identical to that in normal control subjects. In addition, the autophosphorylation of insulin receptors determined at six different insulin concentrations was within the normal range, even when it was expressed as per 300μ
l of erythrocytes as well as per unit receptor. These results demonstrate that insulin resistance in the patient with Werner's syndrome is caused by a defect that cannot be detected by means employed in this study, and suggest that the defect is present at the steps distal to the autophosphorylation of tyrosine kinase of insulin receptors.
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SHIGEKI YABE, MASAMI MURAKAMI, KAYOKO MARUYAMA, HIDEKO MIWA, YUKIHITO ...
1995 Volume 42 Issue 1 Pages
115-119
Published: 1995
Released on J-STAGE: November 21, 2006
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Antipituitary antibodies have been reported to exist in sera of patients with autoimmune endocrine disorders. In order to investigate the pituitary antigens recognized by antipituitary antibodies, we studied the autoantigens in rat pituitary membrane and cytosolic fractions recognized by human antipituitary antibodies and anti-human pituitary hormone antibodies. Sera from 6 patients which showed positive antipituitary antibodies by immunofluorescence methods were studied. Each serum identified some proteins with 14.5, 22, 47, 49, 65, 84 and 97.5kDa. Anti-GH antibodies and anti-PRL antibodies identified a positive band with 22 kDa, suggesting that anti-GH and anti-PRL antibodies may be present in patients' sera. These results indicate that Western blot analysis of rat pituitary antigens recognized by human antipituitary antibodies is a useful method to elucidate the pathophysiology of autoimmune endocrine disorders.
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