Y Shishiba

National Research Institute for Child Health and Development, Tokyo, Edo, Tōkyō, Japan

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Publications (135)183.12 Total impact

  • Yozen Fuse · Yoshimasa Shishiba · Minoru Irie
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    ABSTRACT: Table 3 contains some typographical errors. Median (IQR) of FT4 should be median (5-95th percentile) and the median (IQR) values of TSH are replaced with median (5-95th percentile) values.
    Endocrine Journal 01/2014; 61(7):743. DOI:10.1507/endocrj.ERT14-001 · 2.02 Impact Factor
  • Yozen Fuse · Yoshimasa Shishiba · Minoru Irie
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    ABSTRACT: Iodine is an essential nutrient for thyroid hormone synthesis, and iodine deficiency especially in pregnant and lactating women results in serious damage to their infants. To characterize iodine nutrition throughout gestation by using a food frequency questionnaire (FFQ) and urinary iodine concentration (UIC) measurement, and to establish appropriate gestational age-specific reference ranges for serum TSH and FT4 in thyroid autoantibody (ThAb) negative euthyroid Japanese women, a total number of 563 pregnant women including 422 subjects with negative ThAbs, 105 postpartum women and their 297 newborn infants were included in the study. Dietary iodine intake (DII) was evaluated by FFQ. Serum TSH, FT4 and UIC were sequentially determined in the three trimesters of pregnancy and at the 31st postpartum day. The overall median UICs throughout pregnancy and in the postpartum period were 224.0 and 135.0μg/L, respectively, suggesting sufficient iodine nutrition. The median DII was 842.4μg/day in pregnant women. The median UIC in the first trimester (215.9μg/L) significantly decreased in the second trimester (136.0μg/L). The prevalence of pregnant women with a UIC below 150μg/L was 31.6% and that in lactating women with a UIC below 100μg/L was 33.3%. The pattern of gestational change in serum TSH and FT4 was comparable to that in iodine-sufficient areas. A substantial percentage of women might be at risk for iodine deficiency if there is a restriction of iodine-rich foods. However, iodine supplementation for pregnant women must be carefully balanced against the risk of iodine excess particularly in Japan. Further research in larger samples is needed.
    Endocrine Journal 06/2013; DOI:10.1507/endocrj.EJ13-0184 · 2.02 Impact Factor
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    ABSTRACT: Iodine deficiency in pregnant and lactating women results in serious damage to their fetuses, newborns, and weaning infants. The effect of dietary iodine intake on maternal and infantile thyroid function has not been well studied in iodine-sufficient areas, and there are few data on appropriate gestational age-specific reference ranges for urinary iodine excretion during pregnancy and lactation. The aim of the study was to characterize the gestational change of urinary iodine excretion in Japanese women and to assess the effects of iodine status on thyroid function in mother and infant. A total of 934 Japanese women and their 722 newborn infants were enrolled in the study. Iodine and creatinine concentrations were determined in spot urine samples in the three trimesters of pregnancy and the postpartum period at 34.0 d after delivery. Serum thyroperoxidase antibody and thyroglobulin antibody, TSH, and free T(4) were measured in each trimester, and neonatal TSH was measured on postnatal d 4. The overall median urinary iodine concentration (UIC) during pregnancy was 219.0 μg/liter, higher than that in postpartum women (135.0 μg/liter). The prevalence of pregnant women with low UIC less than 100 μg/liter or high UIC greater than 500 μg/liter was 16.1 and 22.2%, respectively. Urinary iodine excretion decreased from 221.0 μg/liter in the first trimester to 208.0 μg/liter in the second trimester to 193.0 μg/liter in the third trimester, and then remained at 135.0 μg/liter postpartum. [corrected]. The maternal UIC correlated positively with serum TSH during pregnancy. There was no significant difference in UIC between subjects with positive thyroid autoantibodies and those with negative antibodies. Iodine intake assessed by UIC in Japanese pregnant women is regarded as sufficient and not excessive according to World Health Organization criteria. Although the data are local, our results provide additional information on the reference range for UIC throughout gestation in iodine-sufficient areas.
    The Journal of Clinical Endocrinology and Metabolism 09/2011; 96(12):3846-54. DOI:10.1210/jc.2011-2180 · 6.31 Impact Factor
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    ABSTRACT: We examined 2,046 adults (834 males and 1,212 females aged 20-75 years) from polluted district in East Slovakia (POLL) and two neighboring upstream and upwind located districts of background pollution (BCGR). By ultrasound we estimated the thyroid volume (ThV), hypoechogenicity (HYE), nodules and cysts. Serum levels of thyrotropin (TSH), thyroperoxidase antibodies (TPOab) and thyroglobulin were estimated by electrochemiluminiscent assay and these of 15 PCB congeners, p,p'-DDE, p,p'-DDT, hexachlorobenzene (HCB) and hexachlorocyclohexane by high-resolution gas chromatography. In 320 subjects also selected hydroxylated and methylsulfonated PCB metabolites, polychlorinated dibenzo-dioxins (PCDDs), -furans (PCDFs), five dioxin-like coplanar and eight mono-ortho PCB congeners were estimated. Urinary iodine was measured by automatic microplate method. Reciprocal positive association was found between three major POPs (PCBs, DDE and HCB), the levels of these and also PCDDs plus PCDFs in polluted area being considerably higher than in background pollution area. ThV in groups of males and females from POLL with high PCBs level was significantly higher (p<0.001 by t-test) then in age and sex matched groups from BCGR with low PCBs level. In 1,048 males and females aged <60 years with serum PCBs level >1,000 ng g(-1) lipid (median=1,756 ng g(-1)) a significant effect of age on ThV was found (p<0.01 by ANOVA), while in 921 respective subjects with PCBs level <1,000 ng g(-1) (median=661 ng g(-1)) it was not. These findings supported the view on the additional effect of PCBs on ThV other than that of age. Since the urinary iodine in both districts showed optimal range, any interfering effect of unsatisfactory iodine intake on ThV may be excluded. The frequency of autoimmune thyroiditis signs such as HYE, increased serum level of TPOab and TSH resulting in subclinical or overt thyroid hypofunction was positively associated with sex, age and organochlorine levels. The increase of such frequency in males with POPs levels was much more abrupt than that in females. No considerable differences in the frequency of thyroid nodules as related to PCBs level were found.
    Chemosphere 09/2007; 69(1):118-27. DOI:10.1016/j.chemosphere.2007.04.039 · 3.50 Impact Factor
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    ABSTRACT: In a certain area of Michalovce district in East Slovakia, heavy industrial pollution by polychlorinated biphenyls (PCBs) developed in 1955-1984 and very high PCB levels in environmental and human samples are still persisting. Recently, a total of 2045 adults from this and the surrounding background pollution area have been examined using questionnaire data, thyroid volume by ultrasound (ThV), urinary iodine and serum levels of 15 PCB congeners, hexachlorobenzene (HCB), 2,2'-2-bis(4-chlorobiphenyl)-1,1-dichloroethylene (DDE), 2,2'-bis(4-chlorophenyl)-1,1,1-trichloroethane (DDT), alpha-, beta- and gamma-hexachlorocyclohexane (HCH), thyrotropin (TSH), free thyroxine (FT4), anti-thyroperoxidase antibodies (TPOab) and fasting glucose. As based on our previous findings of strikingly high level of PCBs in fish from high pollution area (e.g. mean level of 375430 ng/g lipid) and considerably lower, but still relatively high level in background pollution area (e.g. mean PCB level of 5150 ng/g), the information on the frequency of fish meals and approximate annual consumption of fish from local waters was obtained by questionnaires. The association of contaminated fish consumption with very high blood levels of PCBs, DDE and HCB and increased ThV as well as with increased frequency of positive TPOab, high values of FT4 and impaired fasting glucose (IFG) was found. These associations were also confirmed in 16 marital pairs from high pollution area with very high PCB level in both members associated with high fish consumption. It was concluded that, due to persistent heavy pollution of waters, soil and food chain namely by PCBs, but also by pesticides (e.g. DDE and HCB) resulting from their previous extensive use in agriculture, the fish from local waters still remains the most important source of these toxic pollutants which results in considerable adverse health effects.
    Chemosphere 05/2007; 67(9):S379-85. DOI:10.1016/j.chemosphere.2006.05.132 · 3.50 Impact Factor
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    Yozen Fuse · Nanako Saito · Toshiko Tsuchiya · Yoshimasa Shishiba · Minoru Irie
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    ABSTRACT: Iodine deficiency disorders (IDDs) are serious global public health problems and approximately 2 billion people are at risk of IDD complications. Urine iodine and thyroid size by ultrasound in school-age children are important indicators for assessing IDD in a population. Interpretation of sonographically measured thyroid volume requires valid reference criteria from iodine-sufficient populations, and in 2003 WHO (World Health Organization)/ICCIDD (International Council for the Control of Iodine Deficiency Disorders) proposed new international reference values for thyroid volume in children aged 6-12 years. To establish a normative reference of thyroid volume and characterize the current status of iodine nutrition in Japanese schoolchildren in Tokyo, where iodine deficiency has never existed, a total of 654 subjects aged 6-12 years (317 girls and 337 boys) in three primary schools were enrolled in the study in 2002. Thyroid volume was determined by using the standardized method recommended by WHO/ICCIDD and the iodine concentration in spot urine samples and the anthropometric measurements were evaluated. Thyroid volume was positively correlated with the children's age, height, weight, or BSA. Regardless of gender the computed median and 97th percentile thyroid volumes based on age or BSA in Japanese children were generally lower than the corresponding values recently reported in iodine-sufficient areas, although these values were slightly higher (5-13%) than those in the 2003 WHO/ICCIDD international reference. The computed median value of urinary iodine concentration was 281.6 microg/L (303.7 microg/gCre) and extremely high values exceeding 1,000 microg/L were found in 16% of the subjects. The present study clearly indicated a high iodine intake in Japanese schoolchildren and also established reference values for thyroid volume that might be applicable to countries in the Far East as a population-specific local reference.
    Thyroid 03/2007; 17(2):145-55. DOI:10.1089/thy.2006.0209 · 3.84 Impact Factor
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    ABSTRACT: Goiter prevalence in school-age children is an indicator of the severity of iodine deficiency disorders (IDDs) in a population. In areas of mild-to-moderate IDDs, measurement of thyroid volume (Tvol) by ultrasound is preferable to palpation for grading goiter, but interpretation requires reference criteria from iodine-sufficient children. The study aim was to establish international reference values for Tvol by ultrasound in 6-12-y-old children that could be used to define goiter in the context of IDD monitoring. Tvol was measured by ultrasound in 6-12-y-old children living in areas of long-term iodine sufficiency in North and South America, central Europe, the eastern Mediterranean, Africa, and the western Pacific. Measurements were made by 2 experienced examiners using validated techniques. Data were log transformed, used to calculate percentiles on the basis of the Gaussian distribution, and then transformed back to the linear scale. Age- and body surface area (BSA)-specific 97th percentiles for Tvol were calculated for boys and girls. The sample included 3529 children evenly divided between boys and girls at each year ( +/- SD age: 9.3 +/- 1.9 y). The range of median urinary iodine concentrations for the 6 study sites was 118-288 micro g/L. There were significant differences in age- and BSA-adjusted mean Tvols between sites, which suggests that population-specific references in countries with long-standing iodine sufficiency may be more accurate than is a single international reference. However, overall differences in age- and BSA-adjusted Tvols between sites were modest relative to the population and measurement variability, which supports the use of a single, site-independent set of references. These new international reference values for Tvol by ultrasound can be used for goiter screening in the context of IDD monitoring.
    American Journal of Clinical Nutrition 03/2004; 79(2):231-7. · 6.92 Impact Factor
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    A Takeshita · N Koibuchi · J Oka · M Taguchi · Y Shishiba · Y Ozawa
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    ABSTRACT: There is increasing concern about endocrine-disrupting chemicals (EDCs) which may produce adverse health effects in humans and other species. One such chemical, bisphenol-A (BPA), a monomer of polycarbonate plastics, is widely used in consumer products; it has been reported to contain estrogenic activity through binding to estrogen receptors. Cytochrome P450 mono-oxygenase 3A4 (CYP3A4) is one of the key enzymes for the metabolism of endogenous steroids and foreign chemicals in liver. The orphan nuclear receptor, steroid and xenobiotic receptor (SXR/PXR), has recently been isolated. A variety of known inducers of CYP3A4 bind to SXR/PXR, and stimulate transcription on xenobiotic-response elements (XREs) located in the promoter region of the CYP3A4 gene. Recent study has shown that EDCs, diethylhexylphthalate (DEHP) and nonylphenol, but not BPA, induce mouse SXR/PXR-mediated transcription. However, it is known that species differences in SXR alter CYP3A inducibility. To test whether BPA stimulates human SXR/PXR-mediated transcription using reporter gene assays. Transfection assays were performed with human SXR/PXR expression plasmid and a reporter plasmid containing the XREs in the CYP3A4 gene promoter in HepG2 cells. BPA-induced interaction of human SXR/PXR with steroid receptor coactivator-1 (SRC-1) was analyzed by mammalian two-hybrid assays. BPA, as well as DEHP, activated human SXR-mediated transcription on the XREs. In mammalian two-hybrid assays, BPA recruited SRC-1 to the ligand-binding domain of human SXR/PXR. Our observations have indicated that BPA may be a human-specific inducer of the CYP3A4 gene, and may influence the metabolism of endogenous steroids, drugs, and other xenobiotics.
    European Journal of Endocrinology 11/2001; 145(4):513-7. DOI:10.1530/eje.0.1450513 · 3.69 Impact Factor
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    ABSTRACT: OBJECTIVE We investigated preoperative and postoperative serum α-subunit levels and the α-subunit response to TRH in patients with various types of pituitary tumour and correlated the data with histological findings in order to clarify the significance of α-subunit measurement in pituitary adenomas. PATIENTS We examined 59 patients with pituitary tumours (22 with GH cell adenomas, 30 with clinically nonfunctioning adenomas and seven with other tumours) treated at Toranomon Hospital between 1996 and 1998. RESULTS The basal α-subunit level was supranormal in six out of 22 (27%) patients with a GH cell adenoma and in nine out of 30 (30%) patients with a nonfunctioning adenoma. A paradoxical α-subunit response to TRH was found in seven out of 22 (32%) patients with a GH cell adenoma. These seven patients also showed a paradoxical GH response to TRH administration. In addition, paradoxical response to TRH was found in eight out of 30 (27%) patients with a clinically nonfunctioning adenoma. In contrast, patients with other types of pituitary tumour showed neither a supranormal α-subunit level nor a paradoxical response to TRH. The supranormal α-subunit level and the abnormal response to TRH were normalized in both GH cell adenoma and nonfunctioning adenoma patients after successful surgery. Immunohistochemical studies showed α-subunit positive cells in 51% of GH cell adenomas or nonfunctioning adenomas and there was a good concordance with the serum α-subunit levels in both GH cell adenoma and nonfunctioning adenoma patients. CONCLUSIONS These findings suggest that supranormal serum α-subunit levels are mainly due to hypersecretion by the tumour itself, while the paradoxical α-subunit response to TRH is an associated phenomenon in patients with a GH cell adenoma or nonfunctioning adenoma. The α-subunit level and the response to TRH may be useful indicators for assessing the operative outcome, especially in nonfunctioning adenoma patients who have no other definite endocrine markers.
    Clinical Endocrinology 03/2001; 54(4):479 - 484. DOI:10.1046/j.1365-2265.2001.01174.x · 3.35 Impact Factor
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    ABSTRACT: Myocilin is known to be associated with the pathogenesis of juvenile-onset primary open angle glaucoma. The tissue distribution of myocilin transcripts has been analyzed in both humans and mice, and a high level of expression in the retina and skeletal muscle has been reported. The functions of myocilin in these tissues are unknown. We isolated rat myocilin cDNA and examined the expression pattern of myocilin, including its expression in endocrine organs, using Northern blot analysis. The rat myocilin cDNA sequence has two in-frame initiation codons, the upstream and downstream ATGs corresponding to the initiation codon of human and murine myocilin, respectively. It is most likely that the first ATG is a translational initiation codon, since 8 of 13 amino acid residues deduced from the rat cDNA sequence between the first and the second ATGs are the same as those in human myocilin. The open reading frame encodes 502 amino acids. Rat myocilin also has both a myosin-like domain and an olfactmedin-like domain, which have been identified in human and murine myocilin. Northern analysis of rat myocilin mRNA revealed substantial expression in the thyroid gland, as well as in the retina and muscle. No transcripts were detected in other endocrine glands, including the adrenal gland, pituitary, and testis. Myocilin may play an important role in thyroid function. Further study of the expression and role of myocilin in the thyroid is required.
    Molecular Genetics and Metabolism 06/2000; 70(1):75-80. DOI:10.1006/mgme.2000.2986 · 2.83 Impact Factor
  • Minoru Irie · Yoshimasa Shishiba
    01/2000; 5(4):63-65. DOI:10.5363/tits.5.4_63
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    ABSTRACT: Parathyroid hormone-related protein (PTHrP) is now suspected to act as an autocrine or paracrine regulator of cell growth or differentiation, although it was originally reported as a hypercalcemic substance in malignancies. This study was performed to assess the relationship between PTHrP expression and cell proliferation in human parathyroid glands. The localization of PTH and PTHrP was studied in 42 samples of hyperplastic parathyroid from 14 long-term hemodialysis cases with immunohistochemistry and in situ hybridization. Results were compared with proliferative activity (proliferating cell nuclear antigen index: counts of proliferating cell nuclear antigen-positive cells/100 cells). The localization of the PTH/PTHrP receptor was also examined. Ten normal glands were studied as controls. In hyperplasia, cells positive for PTH, PTHrP, or both were observed immunohistochemically. The areas expressing PTHrP mRNA completely coincided with those positive for PTHrP immunohistochemically. Oxyphilic or transitional oxyphilic cells were consistently positive for PTHrP. PTH/PTHrP receptors were located in the cytoplasmic membrane in most parathyroid cells. Proliferating cell nuclear antigen-positive cells were rare in normal glands with an index of 0. 22 +/- 0.09 (mean +/- sem). They were significantly increased in hyperplastic cases but less for PTHrP-positive than for -negative cells (1.25 +/- 0.16 as compared with 7.80 +/- 0.52; P < 0.0001). The observed low level of proliferation of PTHrP-positive cells suggests a functional role for PTHrP as a possible growth suppressor in the human parathyroid.
    Kidney International 02/1999; 55(1):130-8. DOI:10.1046/j.1523-1755.1999.00230.x · 8.52 Impact Factor
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    ABSTRACT: Familial hyperparathyroidism (FHPT) is a hereditary disease where hyperparathyroidism (HPT) is transmitted in an autosomal dominant fashion. FHPT consists of a variety of diseases such as multiple endocrine neoplasia type1 (MEN 1) and type2 (MEN 2), familial isolated hyperparathyroidism (FIHPT) with single adenoma and with multiple adenomas (or hyperplasia), and FHPT with jaw-tumor (FHPT-JT). Isolation of the genes responsible for MEN1, and 2, i.e. MEN1 and RET, respectively, makes it possible to examine the relations among disorders constituting FHPT. We studied germ-line mutations in these 2 genes in a family of FHPT with single parathyroid adenoma. The disorder in this family was proved to be an entity different from MEN1 because no germ-line mutations in MEN1 gene were found in the affected members. The loss of heterozygosity (LOH) at MEN1 gene and PYGM were not found in the abnormal parathyroid in this family, supporting the above conclusion. No mutations in exons 10, and 11 of RET proto-oncogene was found in germ-line DNA of the affected member of the family, suggesting no relation to MEN2A. Linkage study excluded the possibility of FHPT-JT syndrome. PRAD1 was not overexpressed in the parathyroid tumors in this family. The relation of this disorder to FIHPT with multiple enlarged parathyroid glands remains to be clarified. A search for the gene(s) predisposing to FIHPT is needed.
    Endocrine Journal 11/1998; 45(5):637-46. DOI:10.1507/endocrj.45.637 · 2.02 Impact Factor
  • Yasunori Ozawa · Taeko Shimizu · Yoshimasa Shishiba
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    ABSTRACT: To clarify the clinical significance of elevation of serum aminotransferase levels in anorexia nervosa, we analyzed the relationships of serum aminotransferase levels to other serum biochemistry and physical conditions before and during refeeding therapy in 101 patients with anorexia nervosa. Before refeeding therapy, body mass index (BMI) was distributed from 9.9 to 16.4 kg/m2 (13.2 +/- 1.3, mean +/- SD), and 29 patients (28.7%) showed abnormally high aminotransferase levels. Among 17 patients with a BMI of less than 12 kg/m2, the aminotransferase level was abnormally high in 13 patients (76%). Incidence and severity of serum aminotransferase elevation were greater in the patients with lower BMI. The groups with high serum aminotransferase levels had a lower body temperature, lower pulse rate, and higher incidence of other biochemical abnormalities than the group with normal serum aminotransferase levels. These findings indicate that aminotransferase elevation develops at a high incidence in anorectic patients with a critically life-threatening condition, and it is a sign of multiorgan failure requiring urgent calorie repletion. This type of aminotransferase elevation is to be distinguished from refeeding-induced aminotransferase elevation.
    Internal Medicine 01/1998; 37(1):32-9. DOI:10.2169/internalmedicine.37.32 · 0.97 Impact Factor
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    ABSTRACT: A series of 44 patients with acromegaly underwent transsphenoidal surgery between 1987 and 1996. The early postoperative mean basal GH level < 5 ng/ml or < 3 ng/ml was achieved in 43 (97.7%) or 38 (86.4%) out of 44 patients, respectively. Preoperative abnormal GH secretory response to TRH, GnRH and oral glucose administration was restored to normal both after surgery and at the time of the final follow-up in all patients whose early postoperative mean basal GH levels were reduced to < 3 ng/ ml, whereas they remained abnormal in those with mean basal GH levels of > or = 3 ng/ml. In contrast, insulin-like growth factor 1 (IGF-1) levels, when measured by the extraction method, tended to be reduced gradually to normal between 6 months and 2 years after surgery in some patients with a successful operation. Therefore, 34 (87.1%) out of 39 patients who have been followed up longer than 6 months met the following stringent criteria at the time of the final follow-up: mean basal GH level < 3 ng/ml, a normal IGF-1 level, and normal GH response to TRH, GnRH and oral glucose administration. In this series, the most unfavorable preoperative factor influencing operative outcome is tumor invasion of the cavernous sinus. Our results clearly indicate that selective adenomectomy by transsphenoidal surgery is the therapy of first choice in any patient with acromegaly and that the complete biochemical cure of acromegaly can be achieved in 87% of patients by surgery alone with an acceptable low surgical morbidity.
    Endocrine Journal 06/1997; 44(3):395-402. DOI:10.1507/endocrj.44.395 · 2.02 Impact Factor
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    ABSTRACT: Parathyroid-hormone-related protein (PTHrP) is widely expressed not only in malignant tumors but also in both epithelial and nonepithelial cells of normal tissues. Secreted PTHrP is suspected to act as a paracrine or autocrine regulator. However, little is known about its secretory pathway. To cast light on this question, we studied the intracytoplasmic distribution of parathyroid hormone (PTH) and PTHrP immunohistochemically and immunoelectron microscopically in 10 surgically resected parathyroid adenomas. Double immunostaining was performed using anti-PTH antibody and a newly established anti-PTHrP antibody to reveal the relationship between their two distributions. Additional examination by cell immunoblot assay was performed to determine whether both PTH and PTHrP are secreted simultaneously. Both PTH and PTHrP were actually secreted from individual parathyroid cells simultaneously on cell immunoblot assay. Immunohistochemically, there were two different types of adenoma cells, i.e., one positive only for PTH and the other positive for both PTH and PTHrP. PTH was distributed linearly or fine granularly along the cytoplasmic membrane, whereas PTHrP was distributed diffusely or coarse granularly in the cytoplasm. The intracytoplasmic distributions of PTH and PTHrP often overlapped. Immunoelectron microscopical examination demonstrated that PTHrP co-localized with PTH in the same secretory granules. The results clearly demonstrated that PTHrP can be co-secreted with PTH via a regulated pathway using secretory granules.
    American Journal Of Pathology 04/1997; 150(3):861-71. · 4.60 Impact Factor
  • S Yamada · M Takahashi · M Hara · A Hattori · T Sano · Y Ozawa · Y Shishiba · K Hirata · M Usui
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    ABSTRACT: Previous studies of Pit-1 expression in human pituitary tumours have produced conflicting results. We have studied expression of Pit-1 mRNA in human pituitary adenomas, as well as in normal human and rat pituitaries, and results were compared with clinical, histological, and immunohistochemical features. In addition, expression of GH, PRL, and TSH-beta mRNA was also studied and compared with Pit-1 gene expression. The adenomas consisted of 13 GH cell adenomas, 7 PRL cell adenomas, 3 TSH cell adenomas, 4 ACTH cell adenomas, and 10 clinically non-functioning adenomas. Expression of the Pit-1, its isoforms, and each hormone, was studied using the reverse transcription polymerase chain reaction. Pit-1 mRNA was expressed not only in normal human and rat pituitaries, but also in all GH, PRL and TSH cell adenomas. There was no correlation between Pit-1 transcripts and biological behaviour or histological findings in these three types of adenoma, suggesting that Pit-1 is generally required for the determination of cell phenotype but is insufficient for the regulation of hormonal activity and tumour growth in these pituitary adenomas. In addition, Pit-1 was also expressed in some ACTH cell (2/4) and non-functioning adenomas (7/10). Although there were no GH, PRL or TSH-beta transcripts in Pit-1 mRNA-negative ACTH cell and non-functioning adenomas, PRL mRNA was detected in all Pit-1 mRNA-positive ACTH cell adenomas and GH, PRL and/or TSH-beta mRNA were found in four of seven Pit-1 mRNA-positive non-functioning adenomas. In contrast, Pit-1 mRNA was expressed without any GH, PRL, or TSH-beta transcripts in only three non-functioning adenomas. These data suggest that expression of Pit-1 mRNA in these two types of adenomas can be mainly attributed to the presence of GH, PRL and/or TSH-beta mRNA expressing cells and that true Pit-1 transcripts found in non-functioning adenomas may be a rare event. Moreover, there were two cases which expressed Pit-1 alpha mRNA, but failed to show other Pit-1 isoform mRNA. There were, however, no clinical or histological differences between these two adenomas showing only Pit-1 alpha mRNA and the others expressing both Pit-1 alpha mRNA and other Pit-1 isoform mRNA. Pit-1 mRNA was expressed not only in GH, PRL and TSH cell adenomas but also in other types of adenoma. However, it is suggested that expression of Pit-1 mRNA in most ACTH cell and non-functioning adenomas can be attributed to GH, PRL and/or TSH-beta mRNA expressing cells. Further studies are necessary to elucidate the role of Pit-1 transcripts in the three non-functioning adenomas without GH, PRL and/or TSH-beta mRNA expression.
    Clinical Endocrinology 10/1996; 45(3):263-72. · 3.35 Impact Factor
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    ABSTRACT: Sixty-one of 83 patients with acromegaly treated between 1969 and 1993 were analysed retrospectively to clarify which early postoperative factors were significant predictors of a successful long-term outcome and which preoperative factors significantly influenced the early postoperative results. Of the 61 patients, 30 were operated on before 1987 and 31 afterwards. A successful long-term surgical outcome was defined as a long-term mean basal GH level < 6 mU/l (comparable to < 3 micrograms/l), a normal IGF-I level, and normal GH dynamics. Overall, 59% of patients (37% before 1987 and 81% after) had an early postoperative mean basal GH level < 6 mU/l, and 56% (29% before 1987 and 77% after) met all three of the specified criteria for a successful long-term surgical outcome. Statistical analysis confirmed that GH dynamics and postoperative mean basal GH level < 6 mU/l were significant predictors of the long-term surgical outcome, whereas the postoperative IGF-I level alone was not. On the other hand, abnormal preoperative GH dynamics were normalized in all patients with a postoperative mean basal level < 6 mU/l. In addition, there were no patients showing an unsuccessful long-term outcome in those associated with both the early postoperative mean basal GH level < 6 mU/l and normalization of the IGF-I level. Therefore, measurement of the early postoperative mean basal GH level and the IGF-I level may be an economical and simple guide to predict the long-term surgical outcome. Moreover, multivariate analysis indicated that cavernous sinus invasion was an independent significant factor influencing the early postoperative outcome. Successful long-term surgical outcome may be predicted if early postoperative mean basal GH level is reduced to < 6 mU/l (< 3 micrograms/l) and IGF-I level becomes normal. This study also confirms that early diagnosis and treatment by an experienced endocrinologist and neurosurgeon can improve the operative results in patients with acromegaly.
    Clinical Endocrinology 09/1996; 45(3):291-8. DOI:10.1046/j.1365-2265.1996.8080817.x · 3.35 Impact Factor
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    ABSTRACT: OBJECTIVE Previous studies of Pit-1 expression in human pituitary tumours have produced conflicting results. We have studied expression of Pit-1 mRNA in human pituitary adenomas, as well as in normal human and rat pituitaries, and results were compared with clinical, histological, and immunohistochemical features. In addition, expression of GH, PRL, and TSH-β mRNA was also studied and compared with Pit-1 gene expression.MATERIAL AND METHODS The adenomas consisted of 13 GH cell adenomas, 7 PRL cell adenomas, 3 TSH cell adenomas, 4 ACTH cell adenomas, and 10 clinically non-functioning adenomas. Expression of the Pit-1, its isoforms, and each hormone, was studied using the reverse transcription polymerase chain reaction.RESULTS Pit-1 mRNA was expressed not only in normal human and rat pituitaries, but also in all GH, PRL and TSH cell adenomas. There was no correlation between Pit-1 transcripts and biological behaviour or histological findings in these three types of adenoma, suggesting that Pit-1 is generally required for the determination of cell phenotype but is insufficient for the regulation of hormonal activity and tumour growth in these pituitary adenomas. In addition, Pit-1 was also expressed in some ACTH cell (2/4) and non-functioning adenomas (7/10). Although there were no GH, PRL or TSH-β transcripts in Pit-1 mRNA-negative ACTH cell and non-functioning adenomas, PRL mRNA was detected in all Pit-1 mRNA-positive ACTH cell adenomas and GH, PRL and/or TSH-β mRNA were found in four of seven Pit-1 mRNA-positive non-functioning adenomas. In contrast, Pit-1 mRNA was expressed without any GH, PRL, or TSH-β transcripts in only three non-functioning adenomas. These data suggest that expression of Pit-1 mRNA in these two types of adenomas can be mainly attributed to the presence of GH, PRL and/or TSH-β mRNA expressing cells and that true Pit-1 transcripts found in non-functioning adenomas may be a rare event. Moreover, there were two cases which expressed Pit-1α mRNA, but failed to show other Pit-1 isoform mRNA. There were, however, no clinical or histological differences between these two adenomas showing only Pit-1α mRNA and the others expressing both Pit-1α mRNA and other Pit-1 isoform mRNA.CONCLUSIONS Pit-1 mRNA was expressed not only in GH, PRL and TSH cell adenomas but also in other types of adenoma. However, it is suggested that expression of Pit-1 mRNA in most ACTH cell and non-functioning adenomas can be attributed to GH, PRL and/or TSH-β mRNA expressing cells. Further studies are necessary to elucidate the role of Pit-1 transcripts in the three non-functioning adenomas without GH, PRL and/or TSH-β mRNA expression.
    Clinical Endocrinology 08/1996; 45(3):263 - 272. DOI:10.1046/j.1365-2265.1996.00812.x · 3.35 Impact Factor
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    ABSTRACT: Human interferon beta (IFN-beta) has been used for the treatment of patients with benign and malignant astrocytomas. The effect of IFN-beta on pituitary function, however, has not been precisely evaluated before. In this study the serum levels of various anterior pituitary hormones including GH, PRL, ACTH, and TSH were measured to determine the effects of IFN-beta on pituitary endocrine function in 19 consecutive glioma patients receiving IFN-beta. Daily doses of 3 x 10(6) U of IFN-beta were administered as a 30-min intravenous drip infusion beginning at 0800 h every morning during the first week and then 4 times a week for additional 6 weeks. Blood samples were taken on the day prior to administration as controls (0900 h and 1500 h), and on the first day of administration (0900 h and 1500 h) and after 7 days of administration (0900 h) in order to determine the acute and chronic or integrated effects of IFN-beta on the above pituitary hormones. No significant change in serum concentrations of any of the pituitary hormones examined was observed, suggesting that human natural IFN-beta used for the treatment of gliomas has no significant effect on the secretion of these hormones from the pituitary in these patients.
    Endocrine Journal 07/1996; 43(3):335-8. DOI:10.1507/endocrj.43.335 · 2.02 Impact Factor

Publication Stats

958 Citations
183.12 Total Impact Points

Institutions

  • 2013
    • National Research Institute for Child Health and Development, Tokyo
      Edo, Tōkyō, Japan
  • 2007
    • Toho University
      Edo, Tōkyō, Japan
  • 1972–2000
    • Toranomon Hospital
      Edo, Tōkyō, Japan
  • 1988
    • Tokyo Medical and Dental University
      • Department of Pediatrics
      Edo, Tōkyō, Japan