bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of surgical treatment on secondary hyperaldosteronism and relative hyperinsulinemia in primary hyperparathyroidism
Authors: Kovacs L , Goth MI , Szabolcs I , Dohan O , Ferencz A , Szilagyi G
Published: January 2005

OBJECTIVE: To evaluate the renin-aldosterone system and insulin secretion in hyperparathyroidism and their effects on blood pressure regulation. DESIGN: Studies were carried out on patients with primary hyperparathyroidism (PHPT) prior to and following removal of the parathyroid tumor. METHODS: Sixteen normotensive and euglycemic patients with PHPT were studied. The following parameters were measured: basal and stimulated plasma renin activity (PRA) and aldosterone (ALD) secretion: parathormone (PTH) and serum electrolytes. Insulin and glucose levels were measured during an oral glucose tolerance test. RESULTS: Systolic but not diastolic blood pressure showed a decrease following surgery, from 123.3+/-13.0/80+/-8.6 to 116.7+/-13.5/77.3+/-8.8 mmHg. The decrease in the systolic pressure was not clinically significant. After surgery, both the basal and stimulated PRA and ALD values decreased, and the preoperative pathological values returned to normal: PRA basal: 1.79 --> 0.70 ng/ml/h, P=0.0049; PRA stimulated: 7.76 --> 1.90 ng/ml/h, P=0.0031; ALD basal: 111.5 --> 73.0 pg/ml, P=0.0258; ALD stimulated: 392.5 --> 236.0 pg/ml, P=0.0157. The postoperative decrease in the PRA correlated with the changes in PTH levels (r=0.5442, P < 0.05, n=16) but did not correlate with the changes in serum calcium concentrations. Both the fasting and stimulated insulin levels decreased after surgery but remained within the normal range: insulin fasting: 10.2 --> 5.0 mIU/l, P=0.0218; insulin area under the curve: 5555 --> 3296 mIU/l*min, P=0.0218. There was no correlation between the changes in insulin levels and PTH or ion levels. Sodium, potassium and blood glucose levels remained unaffected by parathyroid surgery. CONCLUSIONS: In a population of normotensive hyperparathyroid patients an increased activity of the renin-aldosterone system related to PTH was found and surgery resulted in a small and insignificant decrease in blood pressure. This change was accompanied by a significant decrease in the activity of the renin-aldosterone system indicating the role of the renin-aldosterone system in the regulation of blood pressure in PHPT. Both fasting and stimulated insulin values decreased following removal of the parathyroid tumor, but with no individual correlation with PTH and calcium levels.
Laparoscopic adrenalectomy: a report on 50 operations
Authors: Filipponi S , Guerrieri M , Arnaldi G , Giovagnetti M , Masini AM , Lezoche E , Mantero F
Published: January 2005

OBJECTIVE: To investigate the feasibility, safety and results of laparoscopic transperitoneal adrenalectomies performed with the patient supine, in patients affected by secreting and silent adrenal lesions. METHODS: Exclusion criteria were suspected adrenal primary malignancies. Fifty patients (33 women and 17 men; mean age 49.6 years, range 19-75 years) underwent 51 laparoscopic adrenalectomies (one bilateral). After complete endocrinological evaluation, computed tomography or magnetic resonance imaging, or a combination thereof, 14 non-secreting adenomas, 13 aldosterone-producing adenomas, 13 cortisol-producing adenomas, eight phaeochromocytomas (one bilateral), one androgen-secreting adenoma, and two metastases were considered eligible for adrenalectomy. In five patients, associated procedures were performed during surgery. RESULTS: The lesions ranged in size from 1.5 to 10 cm. There were no intraoperative complications and no blood transfusions were required. The postoperative course was uneventful and painless in all patients. Mean postoperative hospital stay was 2.5 days. In all hypertensive patients, significant improvement or cure of hypertension was observed at follow-up (mean 18 months). In patients with secreting adenomas, normalization of hormone concentrations was obtained after removal of the tumour. In six patients with incidentaloma, the exaggerated 17-hydroxyprogesterone response to ACTH disappeared after surgery. CONCLUSIONS: Secreting and non-secreting adrenal lesions were treated safely by laparoscopy. Relatively small incidentalomas and subclinical hormonally active tumours can be removed by laparoscopy. Early diagnosis enhances prevention and treatment.
Familial isolated hyperparathyroidism due to multiple adenomas associated with ossifying jaw fibroma and multiple uterine adenomyomatous polyps
Authors: Fujikawa M , Okamura K , Sato K , Mizokami T , Tamaki K , Yanagida T , Fujishima M
Published: January 2005

We describe three siblings with hyperparathyroidism due to multiple parathyroid adenomas without evidence of other endocrinological abnormalities. A 22-year-old woman had two parathyroid adenomas complicated by multiple ossifying jaw fibromas. Her sister, aged 29, also suffered from primary hyperparathyroidism associated with two parathyroid adenomas one of which was also suspected to be a carcinoma. These two female patients had unusual multiple small uterine polyps, which were diagnosed as adenomyomatous polyps. Their brother, aged 17, had two parathyroid adenomas complicated by urolithiasis. These three patients are characterized by young adult-onset familial isolated hyperparathyroidism due to multiple adenomas with various complications including ossifying jaw fibroma and uterine adenomyomatous polyps. These clinical features are different from those of familial hyperparathyroidism associated with multiple endocrine neoplasia.
Transient cold nodule of the thyroid due to localized postpartum thyroiditis
Authors: Luboshitzky R , Qupti G , Ishai A , Dharan M
Published: January 2005

A 27-year-old woman with no previous personal or family history of thyroid disease was referred to us for the evaluation of thyroid nodule, five months postpartum. Thyroid scintigraphy demonstrated a left cold nodule. Fine needle aspiration cytology of the nodule showed a mixture of colloid, follicular cells and lymphocytes, suggesting lymphocytic thyroiditis. Thyroid function tests were normal and thyroid autoantibodies were negative. After two months the thyroid nodule was not palpated and thyroid scintigraphy returned to normal. Thyroid function tests remained normal twelve months after delivery. These findings suggest that postpartum thyroiditis may present as a localized transient form and should be considered in the differential diagnosis of painless solitary nodule that appears postpartum.
Intra-adrenal factors are not involved in the differential control of cortisol and adrenal androgens in human adrenals
Authors: Fearon U , Clarke D , McKenna TJ , Cunningham SK
Published: January 2005

The differential control of adrenal androgens and cortisol may be due to intra-adrenal factors, which may be age- or sex-related, or due to extra-adrenal factors, such as circulating hormones. The purpose of this study was to identify any intrinsic differences that may exist in steroidogenic production occurring within adrenals obtained from males and females, and any maturational differences that may evolve with age. Using human adrenals from 48 transplant donors (32 males, 16 females; ages 5-60 years), the influences of age and sex on basal production of and ACTH-stimulated cortisol, androstenedione and dehydroepiandrosterone (DHEA) were examined in freshly prepared adrenal cell suspensions. Basal and ACTH-stimulated cortisol, androstenedione and DHEA production were similar in adrenals from males and females and did not correlate significantly with age when the whole group was examined. When steroidogenesis in male and female adrenals was examined separately against age, a significant correlation was observed only for basal and ACTH-stimulated androstenedione in adrenals from males in the younger age group, 5-30 years (basal: r=0.84, P=0.0001; ACTH-stimulated: r=0.52, P=0.007). Examination of the relationships between the steroids disclosed that the basal and ACTH-stimulated cortisol/androgen ratios did not correlate significantly with age, but the androstenedione/DHEA ratio showed a significant direct relationship with age in males only (basal: r=0.53, P=0.006; ACTH-stimulated: r=0.5, P=0.01). These data suggest that the influences of sex and age are minor in the modulation of adrenal steroidogenesis and support the concept that extra-adrenal factors dominate in the differential modulation of adrenal androgens and cortisol. The relationship between the androstenedione/ DHEA ratio and increasing age in men is consistent with the recently reported stimulatory effect of testosterone on adrenal steroidogenesis by induction of the conversion of DHEA to androstenedione.
Effect of medroxyprogesterone acetate on sex hormone-binding globulin mRNA expression in the human endometrial cancer cell line Ishikawa
Authors: Misao R , Nakanishi Y , Fujimoto J , Tamaya T
Published: January 2005

To understand the rationale of high-dose medroxyprogesterone acetate (MPA) in the treatment of well-differentiated uterine endometrial cancers, the effect of MPA on intracellular sex hormone-binding globulin (SHBG) mRNA expression in well-differentiated uterine endometrial cancer cell line Ishikawa was determined by competitive reverse transcription-polymerase chain reaction-Southern blot analysis. Estradiol-17beta (E2, 10(-8) mol/l) did not alter SHBG mRNA expression, but the addition of 10(-10) mol/l MPA increased it, while a high concentration of MPA (10(-6) to 10(-5) mol/l) with or without E2 suppressed it. Furthermore. a high dose (10(-6) mol/l) of chlormadinone acetate or danazol with or without E2 significantly suppressed its expression, while MPA was the most effective among the hormones tested. The effect of MPA and the other steroid hormone analogs on SHBG expression was not mediated via the progesterone receptor. These findings suggest that intracellular SHBG suppression might partly contribute to the abolition of the intracellular estrogen-dominant milieu, and may be involved as one of the mechanisms of the antitumoral effects of high-dose MPA on the development and growth of some well-differentiated endometrial cancer cells.
Effect of dehydroepiandrosterone sulfate on interleukin-8 receptor during cervical ripening
Authors: Kanayama N , El Maradny E , Goto J , Terao T
Published: January 2005

We investigated the effects of dehydroepiandrosterone sulfate (DHA-S) on the production of interleukin-8 (IL-8) and expression of the interleukin-8 receptor (IL-8 R) in human cervical tissue. DHA-S increased the levels of IL-8 in cultured human cervical fibroblasts and in the supernatant in a time- and dose-dependent manner. DHA-S induced IL-8 and IL-8 R expression in human cervical fibroblasts and human pregnant cervical tissue at term in a dose-dependent manner. In addition, it induced the expression of IL-8 R in an explant culture of human cervical tissue and cultured human cervical fibroblasts in a time- and dose-dependent manner. However, dehydroepiandrosterone (DHA) only slightly induced the production of IL-8 and the expression of IL-8 R in the same cells and tissue. These results suggest that DHA-S up-regulates the autocrine system of IL-8 through the expression of IL-8 R.
The role of tyrosine kinase in gonadotropin-induced ovulation in the rat ovary
Authors: Shimamoto T , Yamoto M , Nakano R
Published: January 2005

OBJECTIVES: Our purpose was to elucidate the involvement of the tyrosine kinase pathway in gonadotropin-induced ovulation in the rat ovary. STUDY DESIGN: We investigated the effect of a tyrosine kinase inhibitor, tyrphostin, on the rat ovulatory process in vivo and in vitro. METHODS: In cultured rat granulosa cells, the effect of tyrphostin on LH-, dibutyryl cyclic AMP ((Bu)2cAMP)- or forskolin-stimulated tissue type plasminogen activator (tPA) activities was examined by using a fibrin autography technique. In an in vivo system, tyrphostin was injected into the bursal cavity of the ovary in pregnant mare serum gonadotropin-treated rats, just before human chorionic gonadotropin administration. After 24 h, the number of oocytes in the oviduct was counted and the tyrphostin-treated ovaries were examined histologically. RESULTS: Tyrphostin inhibited LH-stimulated tPA activity but did not affect (Bu)2cAMP- or forskolin-stimulated ones. In an in vivo study, tyrphostin suppressed oocyte release dose-dependently. Histological observations revealed that tyrphostin-treated ovaries contained many large unruptured follicles and a few corpora lutea. CONCLUSION: This study suggests that the suppressive effect of tyrphostin on ovulation may be partly due to tPA activity inhibition in the granulosa cells via the suppression of tyrosine kinase activity. Additionally, tyrosine kinase phosphorylation may be involved in gonadotropin-activated signaling systems in the rat ovulatory process.
Gender-specific relationship between serum free and total IGF-I and bone mineral density in elderly men and women
Authors: Janssen JA , Burger H , Stolk RP , Grobbee DE , de Jong FH , Lamberts SW , Pols HA
Published: January 2005

OBJECTIVE: Little is known about the association between free IGF-I levels and bone mineral density (BMD). DESIGN: A cross-sectional study of 218 healthy subjects (103 men, 115 women, age 55-80 years) was carried out. METHODS: Fasting serum free IGF-I, total IGF-I, estradiol and sex hormone-binding globulin (SHBG) levels were measured. The ratio of estradiol to SHBG was used as an index of free estradiol. BMD measurements were performed by dual-energy X-ray absorptiometry of the lumbar spine and the proximal femur. RESULTS: In multivariate analyses with BMD of the lumbar spine as the dependent variable and serum free IGF-I, age, body mass index (BMI) and the free estradiol index as independent variables, the free IGF-I was positively related to the BMD of the lumbar spine in men (P = 0.02) but not in women. When the same analyses for the lumbar BMD were performed with total serum IGF-I the association was also only statistically significant in men (P = 0.05). In multivariate analyses with the trochanter BMD as the dependent variable and serum free IGF-I, total IGF-I, age, BMI and the free estradiol index as independent variables, the associations between (free and total) IGF-I and the trochanter BMD in men was of borderline significance. CONCLUSIONS: In elderly men free and total IGF-I were positively related to lumbar BMD, while (free and total) IGF-I was borderline positively related to trochanter BMD. As these relationships were not observed in elderly women, we suggest a weak gender-specific anabolic effect of IGF-I on BMD on trabecular bone.
Modulating effect of human growth hormone on tumour necrosis factor-alpha and interleukin-1beta
Authors: Bozzola M , De Amici M , Zecca M , Schimpff RM , Rapaport R
Published: January 2005

We measured serum tumour necrosis factor-alpha (TNF-alpha) as well as interleukin-1betta (IL-1beta) and GH concentrations in 15 children with isolated growth hormone deficiency (GHD), age range 5.1-13.9 years, before and 4 and 24h after the first GH injection (0.1 IU/kg s.c.). No differences were found in basal concentrations of serum TNF-alpha and IL-1beta between GHD children (10.01 +/- 1.55 pg/ml and 2.14 +/- .16 ng/ml respectively) and sex- and age-matched controls (11.57 +/- 2.16 pg/ml and 3.78 +/- 1.46 ng/ml respectively). In GHD children, serum TNF-alpha and IL-1beta values had significantly increased (P < 0.002) 4h (26.75 +/- 5.57 pg/ml and 2.99 +/- 0.21 ng/ml respectively) and decreased again 24 h after GH administration. Likewise, serum GH levels had significantly increased 4 h (from 1.29 +/- 0.69 to 48.71 +/- 13.35 ng/ml, P < 0.001) and decreased to basal values 24h after GH administration. A significant correlation was found between basal serum concentrations of GH and those of both TNF-alpha (P < 0.01) and IL-1beta (P < 0.05). However, no correlation was found between serum GH concentration and either TNF-alpha or IL-1beta levels 4 and 24h after GH administration. Our data suggest that GH plays a role in modulating TNF-alpha and IL-1beta release in humans.
Hyperleptinaemia is associated with impaired gonadotrophin response to GnRH during late puberty in obese girls, not boys
Authors: Bouvattier C , Lahlou N , Roger M , Bougneres P
Published: January 2005

In ob/ob mice, leptin deficiency results in hypogonadotrophic hypogonadism, impaired sexual maturation and infertility, which are all corrected by leptin administration. In humans, pubertal development and menarche are related to the attainment of a critical amount of body fat. To examine whether changes in circulating concentrations of leptin could be a hormonal signal influencing gonadotrophin secretion, we studied 98 adolescents and young adults of both sexes, aged 13-19 years, whose weight varied from normal to massively obese and whose sexual maturation was between Tanner stages 3 and 5. We measured leptin, sex steroids and circulating gonadotrophin concentrations in the basal state and in response to GnRH. In perimenarchial and young adult girls, we found that the LH and FSH responses to GnRH were negatively correlated with body mass index (BMI: r = -0.45 and -0.47 respectively, P < 0.0025) and circulating leptin (r = -0.53 and -0.49 respectively, P < 0.002). Decreased LH and FSH responses to GnRH were associated with increased adiposity and hyperleptinaemia. Our data do not establish, but are consistent with a direct neuroendocrine negative effect of excess leptin on the central reproductive system of obese girls. In boys of comparable adiposity, we found no influence of BMI or leptin on gonadotrophin concentrations, which is another aspect of the sexual dimorphism characterizing human leptin physiology.
Markers of bone turnover in patients with differentiated thyroid cancer with and following withdrawal of thyroxine suppressive therapy
Authors: Toivonen J , Tahtela R , Laitinen K , Risteli J , Valimaki MJ
Published: January 2005

OBJECTIVE: To study whether levothyroxine (LT4) suppressive therapy exposes patients with differentiated thyroid cancer (TC) to an increased risk of osteoporosis. DESIGN AND METHODS: Markers of bone formation (serum alkaline phosphatase (ALP), osteocalcin (OC), type I procollagen carboxyterminal (PICP) and aminoterminal (PINP) propeptide) and resorption (serum type I collagen carboxyterminal telopeptide (ICTP) and urine hydroxyproline (HOP)), as well as serum intact parathyroid hormone (PTH), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D (1,25(OH)2-D) were measured in 29 patients (25 women, 4 men) with a median age of 45 years, and in 38 age- and sex-matched controls. In a subgroup of 14 patients the measurements were repeated after 5 weeks' interruption of LT4 therapy. Since the primary treatment of TC the patients had used TSH suppressive doses of LT4 (a mean daily dose of 215 microg) for 9 to 11 years. The bone mineral density (BMD) of patients and controls was measured by dual energy X-ray absorptiometry. RESULTS: When on T4 therapy, patients had significantly higher mean levels of ALP (+21%, P < 0.05), OC (+35%, P < 0.01), PICP (+10%, P < 0.05), PINP (+46%, P < 0.001), ICTP (+21%, P < 0.05), and HOP (+37%, P < 0.001) compared with controls. After stopping treatment, OC (-42%, P < 0.001), PINP (-7%, P < 0.05), and ICTP (-54%, P < 0.001) decreased, whereas PICP (+24%, P < 0.001) and 1,25(OH)2D (+29%, P < 0.01) increased. BMD of the lumbar spine and the upper femur was similar in patients and controls. CONCLUSIONS: Patients with differentiated TC have high bone turnover when on LT4 suppressive therapy, After withdrawing treatment both bone formation and resorption decrease acutely. During development of hypothyroidism, serum PICP and PINP, which form from the same type I procollagen molecule and should change similarly, behaved differently. This may be due to different effects of hypothyroidism on their removal through separate receptors in the liver.
Influence of dietary habits on thyroid status of a nomadic people, the Bororo shepherds, roaming a central African region affected by severe iodine deficiency
Authors: Biassoni P , Ravera G , Bertocchi J , Schenone F , Bourdoux P
Published: January 2005

OBJECTIVE: In contrast with the endemic goiter reported in several African countries, the nomadic Bororos of the Central African Republic have an unexpectedly low prevalence of goiter. This study was conducted to elucidate this puzzling observation. DESIGN: Thyroid function and iodine and thiocyanate intakes were evaluated in Bororos and inhabitants of the same area and compared with an Italian population. RESULTS: Urinary iodine concentrations indicated moderate iodine deficiency in the rural people and the Bororos. In the latter, no individual with clinical hypothyroidism was observed. Compared with the reference population, the Bororos had slightly lower thyroxine (T4) and free thyroxine (FT4), slightly increased tri-iodothyronine (T3) and T3/T4 ratio, slightly higher TSH, normal serum thyroglobulin, a prevalence of goiter of 17.1% and a higher urinary thiocyanate. The rural people showed striking differences: lower T4 and FT4, increased T3/T4 ratio, markedly increased TSH and thyroglobulin, a prevalence of goiter of 76.9% and a high urinary thiocyanate, indicating frequent consumption of cassava. A dietary survey indicated that the Bororos ingest large amounts of milk and related products but infrequently eat cassava. CONCLUSION: A minute difference in iodine deficiency between two populations induces totally different patterns of goiter and thyroid function. The reason for such a contrast probably involves differences in diet.
Lack of association of Graves' disease with the A2 allele of the interleukin-1 receptor antagonist gene in a white European population
Authors: Muhlberg T , Kirchberger M , Spitzweg C , Herrmann F , Heberling HJ , Heufelder AE
Published: January 2005

OBJECTIVE: To assess whether the A2-type IL-1RA polymorphism is associated with Graves' disease and Graves' ophthalmopathy. Several reports have described a genetic association between the A2 allele of the interleukin-1 receptor antagonist (IL-1RA) gene and certain inflammatory and autoimmune diseases, suggesting that certain loci within the IL-1-related genes may modulate the autoimmune inflammatory response. Recently, we demonstrated marked differences in the expression and regulation of IL-1RA gene and protein between orbital fibroblasts derived from patients with active Graves' ophthalmopathy and healthy individuals. DESIGN: A total of 144 white European patients with Graves' disease were genotyped to compare their IL-1RA A2 allele frequency with that of 174 healthy controls. METHODS: The polymerase chain reaction was used to amplify the pentallelic variable-number tandem-repeat locus in intron 2 of the IL-1RA gene. RESULTS: We found no significant differences in IL-1RA A2 allele frequencies (0.20 and 0.26 respectively) and IL-1RA A2 carriage rates (31% and 40% respectively) between patients with Graves' disease and the control group. Moreover, presence or absence of Graves' ophthalmopathy in patients with Graves' disease was not related to significant differences in IL-1RA A2 allele frequencies and IL-1RA A2 carriage rates. CONCLUSIONS: Our data do not support an association between the IL-1RA A2 allele and Graves' disease or Graves' ophthalmopathy in our study population. Thus the A2-type IL-1RA gene polymorphism does not appear to indicate an increased susceptibility to develop Graves' disease and Graves' ophthalmopathy. Mechanisms unrelated to the IL-1RA A2 allele may be responsible for altered IL-1RA production within the orbital tissues in Graves' ophthalmopathy.
Identification of a single cytosine base insertion mutation at Arg-597 of the beta subunit of the human epithelial sodium channel in a family with Liddle's disease
Authors: Inoue T , Okauchi Y , Matsuzaki Y , Kuwajima K , Kondo H , Horiuchi N , Nakao K , Iwata M , Yokogoshi Y , Shintani Y , Bando H , Saito S
Published: January 2005

We describe a family with Liddle's disease caused by a novel mutation of the beta subunit of the human epithelial sodium channel (ENaC). A 15-year-old Japanese female was referred to our outclinic because of hypertension. The physical examination showed no abnormal findings except mild hypertension, but the laboratory data revealed low levels of plasma renin activity, plasma aldosterone and serum potassium. A comprehensive analysis of steroid hormones showed only high levels of urinary free cortisol and 17-hydroxycorticosteroids. During loading tests, blood pressure and serum potassium responded well to triamterene and slightly to spironolactone, but did not respond to dexamethasone. In addition, the normal ratio of tetrahydrocortisol plus 5alpha-tetrahydrocortisol to tetrahydrocortisone in a 24 h urinary excretion test strongly suggested a diagnosis of Liddle's disease rather than apparent mineralocorticoid excess syndrome. DNA sequence analysis of members of this family revealed a single cytosine base insertion at Arg-597 of the beta human ENaC in the proband and her mother, leading to a loss of the last 34 amino acids from the normally encoded protein as the result of a frameshift. We conclude that a de novo cytosine insertion into the final exon of the C-terminus of the beta human ENaC is responsible for Liddle's disease in this Japanese family.
Prolonged elimination of tolbutamide in a premature newborn with hyperinsulinaemic hypoglycaemia
Authors: Christesen HB , Melander A
Published: January 2005

So far, gestational diabetes treated with tolbutamide has never been associated with severe hypoglycaemia in the newborn when the mother's diabetes was well controlled. We report a case of a premature neonate, gestational age 34 weeks, with severe and long-standing hypoglycaemia from birth. The mother had well-controlled gestational diabetes, treated with tolbutamide from the 24th week of gestation until delivery. The neonate had inappropriately high levels of serum proinsulin, insulin and C-peptide relative to blood glucose concentrations. From day 19 after birth, the levels were normalized. Serum tolbutamide was 140.6 micromol/l (38 microg/ml) at 3 h after birth. Zero-order kinetics were seen during the first 90 postnatal hours. The half-life of serum tolbutamide decreased from 46 to 6 h. It is suggested that tolbutamide, when given to the mother until delivery, may cause severe and prolonged hyperinsulinaemic hypoglycaemia in premature neonates. The initially prolonged tolbutamide half-lives and zero-order kinetics suggest immaturity of hepatic elimination during the first 2 days of postnatal life.
Identification and initial characterization of stathmin by the differential display method in nerve growth factor-treated PC12 cells
Authors: Takekoshi K , Nomura F , Isobe K , Motooka M , Nammoku T , Nakai T
Published: January 2005

The differential display of mRNA is a new strategy to identify genes that are differentially expressed under altered conditions. We applied this method to determine differential gene expression in the rat pheochromocytoma cell line during differentiation induced by nerve growth factor (NGF). Three different mRNA species were isolated, and their differential expression was confirmed by RT-PCR. One of the mRNA species was identified as stathmin, a 19 kDa cytosolic protein attracting increasing interest for its role in signal transduction. In the NGF-treated PC12 cells, the expression of stathmin mRNA increased in a time-dependent manner, as assessed by northern blot analysis and RT-PCR. We also assessed by northern blot analysis how the expression of stathmin mRNA was altered in human pheochromocytomas (n = 5) compared with that in normal adrenal medulla tissue (n = 5). The mRNA concentrations were found to be significantly greater in the pheochromocytomas than in the normal tissues. It has been shown that stathmin mRNA concentrations are increased in various tumor cells. As pheochromocytomas are well-differentiated tumors of neural origin, it is not unexpected that stathmin mRNA is overexpressed in these tumors. Stathmin was isolated and identified as a differentially expressed gene by the differential display method in PC12 cells during differentiation induced by NGF. In addition, stathmin mRNA was found to be overexpressed in human pheochromocytomas. The mechanisms responsible for the up-regulation of stathmin mRNA during differentiation of PC12 cells and the significance of its overexpression in human pheochromocytomas remain to be determined.
Effects of marginal iodine deficiency on thyroid hormone production, distribution and transport in nonpregnant and near-term pregnant rats
Authors: Versloot PM , Schroder-van der Elst JP , van der Heide D , Boogerd L
Published: January 2005

During pregnancy maternal thyroid hormones are of great importance for normal development of the central nervous system of the fetus. Iodine deficiency of the mother carl result in an impaired development of the fetal brain. In large areas of the world iodine intake is moderately low. To study the effects of marginal iodine deficiency (MID) on the production, distribution, and transport of thyroxine (T4) and 3,5,3'-tri-iodothyronine (T3) in nonpregnant and near-term pregnant rats we performed kinetic experiments (three-compartment analysis). Despite unchanged plasma T4 and T3 during MID, the production and plasma clearance rates of T4 decreased 30% (P = 0.01) in MID nonpregnant (MID-C) rats. For T3, the plasma clearance rate was increased 70% (P = 0.046), while the T3 production was more than doubled (P = 0.042) in MID-C rats. In MID near-term pregnant rats T3 production was decreased 20% (P = 0.04). Hepatic deiodinase type I activity increased during MID in both nonpregnant and pregnant rats. It appears that during MID, rats are able to maintain their euthyroid status. The pronounced increase in transport of T4 from plasma to the fast pool observed in pregnant rats on a normal iodine diet did not occur during MID. In conclusion, in rats MID affects maternal thyroid hormone metabolism, thus influencing the availability of maternal T4 for the fetus.
Dehydroepiandrosterone sulfate does not prevent spontaneous and iodine-induced lymphocytic thyroiditis and diabetes mellitus in the BB/Wor rat
Authors: Alex S , Braverman LE , Fang SL , Norvell B , Robinson S , Franz C , Longcope C
Published: January 2005

Chronic feeding of dehydroepiandrosterone (DHEA) and its sulfated metabolite, dehydroepiandrosterone sulfate (DHEAS), has previously been reported to decrease hyperglycemia, obesity, cancer, and autoantibody generation in a number of animal models and to increase muscle mass and physiological and psychological well-being in elderly humans, although these latter studies remain controversial. The present study was carried out to determine whether large amounts of DHEAS given orally would prevent the occurrence of spontaneous and iodine-induced autoimmune lymphocytic thyroiditis (LT) and/or spontaneous insulin-dependent diabetes mellitus (DM) in male and female BB/Wor rats. DHEAS was administered by gavage (44 mg/rat/day) or in the chow (133 mg/rat/day) to LT- and DM-prone rats from 30 to 120 days of life; some of these rats also received iodine in the drinking water to enhance the incidence and intensity of LT. Onset of DM requiring protamine zinc insulin and its maintenance dose were assessed. Rats were killed at 90 or 120 days of age and blood, thyroid, adrenals, pancreases, testes, and ovaries were removed. Serum glucose, DHEA, DHEAS, thyroxine (T4), tri-iodothyronine (T3) and thyrotropin (TSH) concentrations were measured in all rats in both experiments. Serum DHEAS concentrations were 10-fold higher in the rats given the steroid by gavage or in the diet compared with levels in control rats. DHEAS administered over a prolonged period of time had no significant effect on body weight, incidence and severity of DM, incidence and intensity of spontaneous and iodine-induced LT, and thyroid, pancreas and testes weights but did significantly decrease adrenal and ovarian weights. Serum T4, T3, and TSH concentrations were similar in control and DHEAS-treated rats. In conclusion, DHEAS did not prevent the occurrence of iodine-induced or spontaneous autoimmune LT or spontaneous DM in the BB/Wor rat, at variance with its reported immunosuppressive effects in other animal models.
Biochemical markers of bone metabolism in benign human osteopetrosis: a study of two types at baseline and during stimulation with triiodothyronine
Authors: Bollerslev J , Ueland T , Grodum E , Haug E , Brixen K , Djoseland O
Published: January 2005

Biochemical markers of bone remodelling were used to evaluate bone turnover in two types of autosomal dominant osteopetrosis (ADO) at baseline and during stimulation with triiodothyronine (T3). Eight patients with Type I (aged 23-61 years, mean 40.4 years) and nine patients with Type II ADO (aged 20-49 years, mean 32.8 years) were compared with 10 normal controls (aged 22-54 years, mean 35.4 years). The participants were treated with 100 microg T3 daily for 7 days and followed for a total of 16 weeks. Serum concentrations of T3 increased and corresponding suppression of TSH was observed in all participants. Both formative and resorptive bone markers were normal at baseline. After stimulation with T3, a significant increase was seen in all groups for the formative markers used. Secondary increments were observed at the end of the observation period for all groups, indicating activation of bone remodelling. A variety of resorptive markers was assessed, but no differences between patients and controls were seen. After stimulation, highly significant responses were found in all parameters in all groups, in accordance with stimulation of existing resorptive cells. However, no secondary increments were seen at the end of the observation period. A more pronounced response was found in crosslinks-related assays. The study demonstrates that it is possible to stimulate bone resorptive and formative cells with thyroid hormones in both types of ADO. Moreover, it indicates that the remodelling process is activated by a short course of T3 treatment.
Autoantibodies to thyroid peroxidase in patients with type 1 diabetes in Taiwan
Authors: Chang CC , Huang CN , Chuang LM
Published: January 2005

OBJECTIVE: Type 1 diabetes mellitus is frequently associated with autoimmune thyroid disease (ATD). Genetic susceptibility to autoantibody formation in association with ATD and type 1 diabetes mellitus has been described with varying frequencies, but there is still debate about the situation in the Chinese population. We have, therefore, investigated the prevalence of anti-thyroid peroxidase (anti-TPO) in type 1 diabetic patients, and compared the effect of anti-glutamate decarboxylase (anti-GAD) on the thyroid autoimmunity in patients with type 1 diabetes mellitus in Taiwan. SUBJECTS AND METHODS: Two hundred and forty-three subjects with type 1 diabetes mellitus and seventy unrelated normal controls were recruited for the detection of anti-TPO. Two hundred and seventeen sera from two hundred and forty-three type 1 diabetic patients were tested for anti-GAD. RIA and immunoprecipitation were used for anti-TPO and anti-GAD detection respectively. RESULTS: The intra-assay and interassay coefficients of variation of anti-TPO detected by the RIA method ranged from 5.5% to 11.1%. Among 243 type 1 diabetic patients, 53 (21.8%) were positive for anti-TPO. Compared with those without thyroid autoimmunity, there was a female preponderance for the type 1 diabetic patients with thyroid autoimmunity (female:male, 99:91 vs 37:16 respectively). Among the type 1 diabetic patients with thyroid autoimmunity, anti-TPO tended to occur in those of older age or with long-standing disease. The frequency of anti-GAD was 45.6%, (99 of 217), without gender preponderance (males:females, 18.0% vs 27.61%). Compared with those with negative anti-GAD, no significant difference of anti-TPO positivity for the type 1 diabetic patients with positive anti-GAD was found. CONCLUSION: Our data indicated that the RIA method for anti-TPO detection is sensitive and precise for routine clinical use. The presence of anti-TPO in 21.8% of our type 1 diabetic patients confirmed the strong association of ATD and type 1 diabetes mellitus without ethnic differences. The absence of correlation between anti-TPO and anti-GAD in our type 1 diabetic patients suggested genetic heterogeneity in the role of autoimmunity of type 1 diabetes mellitus and ATD among races.
Leptin levels in non-obese and obese children and young adults with type 1 diabetes mellitus
Authors: Verrotti A , Basciani F , Morgese G , Chiarelli F
Published: January 2005

OBJECTIVE: To evaluate serum leptin levels in children and young adults with type 1 (insulin-dependent) diabetes mellitus and to investigate whether they are different in prepuberty, puberty and young adulthood. DESIGN: Three groups of diabetics (prepubertal, pubertal and young adults) subdivided into obese and non-obese were studied. Three groups of healthy subjects matched for sex, age and body mass index served as controls. RESULTS: Diabetic patients had serum leptin concentrations similar to those of controls in all three groups. A small non-significant increase in leptin from the prepubertal to the young adult age group for both diabetics and controls was found. A significant association of serum leptin level with body mass index (P < 0.001), female sex (P < 0.001) and age (P < 0.01) in both the diabetic and control group was present. Insulin-dependent diabetes was not associated with higher leptin concentration. CONCLUSIONS: Serum leptin concentrations are similar in diabetic patients and healthy controls. The association between obesity and leptin concentration was similar in the diabetic and non-diabetic subjects. Type 1 diabetes mellitus does not modify serum leptin concentration.
Is maternal growth hormone essential for a normal pregnancy?
Authors: Curran AJ , Peacey SR , Shalet SM
Published: January 2005

OBJECTIVE: It remains uncertain whether there is any disadvantage imposed upon women with pituitary disease who are GH-deficient and become pregnant. The aim of this study was to determine whether maternal GH deficiency adversely affects the outcome of pregnancy. DESIGN: Retrospective study. METHODS: The case notes of 77 female patients with known GH deficiency were examined. Sixteen patients (a total of 25 pregnancies) were identified who had been pregnant whilst known to be GH-deficient. Peak GH response to provocative testing prior to pregnancy, length of gestation, birth weight, maternal well-being and the incidence of maternal and fetal complications of pregnancy were documented. RESULTS: Peak GH response to insulin tolerance test (n = 21 ) or glucagon stimulation test (n = 4) prior to pregnancy was 8.7 (< 1 to 17.3)mU/l (peak < or =9 mU/l in 14 cases). There were 25 pregnancies resulting in 26 live births (including one set of twins and one set of quins) and 4 spontaneous first trimester abortions. Eight pregnancies were achieved by ovulation induction. Median gestation of live births was 39 (33 to 42) weeks. Median birth weight excluding multiple births (n = 19), uncorrected for gestational age, was 3.09 (1.64 to 4.19) kg, and the numbers with birth weights below the 10th, between the 10th and 90th, and above the 90th centiles were five, nine and five respectively. Preeclampsia occurred in two pregnancies and post-partum haemorrhage after one pregnancy. There were three minor congenital abnormalities. CONCLUSIONS: Our data suggest that pregnancy in GH-deficient females is not detrimental to the fetus and the incidence of maternal morbidity is low. We conclude that GH replacement therapy is probably not essential for GH-deficient females during pregnancy.
A comparative study of p53 immunoexpression in parathyroid hyperplasias secondary to uremia, primary hyperplasias, adenomas and carcinomas
Authors: Kayath MJ , Martin LC , Vieira JG , Roman LM , Nose-Alberti V
Published: January 2005

OBJECTIVE: To investigate immunoexpression of p53 in parathyroid tumors and hyperplasias and correlate it with the histopathological diagnosis and severity of hyperparathyroidism. DESIGN: A total of 102 parathyroid tissues from archival paraffin-embedded specimens or obtained at surgery between 1988 and 1997 from 65 consecutive individuals with hyperparathyroidism were studied. METHODS: p53 immunoexpression, gland mass, preoperative serum calcium and intact parathyroid hormone (PTH) were analyzed; 14 normal parathyroid glands were used as controls. RESULTS: The histopathological findings were: adenomas (n = 28), primary hyperplasias (n = 12), secondary nodular and diffuse hyperplasias (patients with uremia, n = 57), carcinomas (n = 4) and carcinomatous metastatic tissue (n = 1). Nuclear p53 was detected in 36% of the adenomas, 42% of the primary hyperplastic glands, 72% of the diffuse hyperplasias, 44% of nodular hyperplasias and 40% of the carcinomatous tissues, and was absent from normal glands. p53 expression was significantly more frequent in diffuse hyperplasias than in adenomas (P = 0.037). Serum ionized calcium tended to be higher in p53-positive glands in all histopathological groups; however, the difference was only significant in nodular hyperplasias (P = 0.018). The same trend was observed for serum intact PTH levels of adenomas and nodular hyperplastic glands. Gland mass was not significantly different according to p53 staining. CONCLUSIONS: p53 immunoexpression was not useful in differentiating between the histopathological parathyroid subgroups. p53 immunodetection was particularly frequent in secondary hyperplastic glands of uremic patients. Our study suggests that p53, whether wild-type or mutant, is regulated in parathyroid tumors and hyperplasias. Changes in wild-type p53 may be part of a cellular response to a hyperproliferative condition.
Relationships between neuroradiological and clinical features in apparently idiopathic hypopituitarism
Authors: Arrigo T , De Luca F , Maghnie M , Blandino A , Lombardo F , Messina MF , Wasniewska M , Ghizzoni L , Bozzola M
Published: January 2005

In this study, perinatal history, postnatal auxological and clinical evolution and endocrine features were retrospectively evaluated in 49 children, adolescents and young adults with apparently idiopathic hypopituitarism. They were divided into two groups according to magnetic resonance images: 32 patients with isolated pituitary hypoplasia (group A) and 17 with pituitary stalk interruption syndrome (group B). The aim of the study was to assess whether these neuroradiological pictures are associated with specific endocrine and clinical patterns. No significant difference in terms of gestational age, intrauterine growth and rates of adverse perinatal events was found between the two groups. Clinical signs documenting the existence of pituitary dysfunction in utero or shortly after birth were either slightly (micropenis, cryptorchidism, cholestatic jaundice) or significantly (hypoglycemia) more frequent in patients in group B. Although diagnosis of hypopituitarism was made significantly earlier in patients in group B, height deficiency at diagnosis was similar in both groups. Endocrine investigations revealed a more severe and widespread impairment of pituitary function among those in group B. The main conclusion is that the postnatal clinical course is more severe when growth hormone deficiency is associated with pituitary stalk interruption syndrome than when the pituitary is only reduced in height, probably because of the more severe and widespread impairment of pituitary function in the former cases.
Molecular genetic study in two patients with congenital hypoaldosteronism (types I and II) in relation to previously published hormonal studies
Authors: Peter M , Bunger K , Drop SL , Sippell WG
Published: January 2005

We performed a molecular genetic study in two patients with congenital hypoaldosteronism. An original study of these patients was published in this Journal in 1982. Both index cases, a girl (patient 1) and a boy (patient 2). presented with salt-wasting and failure to thrive in the neonatal period. Parents of patient 1 were not related, whereas the parents of patient 2 were cousins. Endocrine studies had shown a defect in 18-oxidation of 18-OH-corticosterone in patient 1 and a defect in the 18-hydroxylation of corticosterone in patient 2. Plasma aldosterone was decreased in both patients, whereas 18-OH-corticosterone was elevated in patient 1 and decreased in patient 2. Plasma corticosterone and 11-deoxycorticosterone were elevated in both patients, whereas cortisol and its precursors were in the normal range. According to the nomenclature proposed by Ulick, the defects are termed corticosterone methyl oxidase (CMO) deficiency type II in patient 1, and type I in patient 2 respectively. Genetic defects in the gene CYP11B2 encoding aldosterone synthase have been described in a few cases. In patient 1, we identified only one heterozygous amino acid substitution (V386A) in exon 7, which has no deleterious effect on the enzyme activity. In patient 2 and his older brother, we identified a homozygous single base exchange (G to T) in codon 255 (GAG), causing a premature stop codon E255X (TAG). The mutant enzyme has lost the five terminal exons containing the haem binding site, and is thus a loss of function enzyme. This is only the second report of a patient with CMO deficiency type II without a mutation in the exons and exon-intron boundaries, whereas the biochemical phenotype of the two brothers with CMO deficiency type I can be explained by the patient's genotype.
Effects of IGF-I on cardiac growth and expression of mRNAs coding for cardiac proteins after induction of heart hypertrophy in the rat
Authors: Donath MY , Zierhut W , Gosteli-Peter MA , Hauri C , Froesch ER , Zapf J
Published: January 2005

Adult rat cardiomyocytes in long-term culture reexpress several fetal cardiac proteins which also reappear during overload heart hypertrophy in vivo. IGF-I decreases reexpression of some of these proteins and stimulates myofibrillogenesis. IGF-I might therefore contribute to enhancing readaptation of the heart to overload. In order to test this hypothesis, hypertension was induced in male Wistar Kyoto rats by constriction of the left renal artery, and an infusion of 500 microg/day of recombinant human IGF-I (rhIGF-I) or vehicle was started after the operation via intraabdominally implanted osmotic minipumps. In the vehicle-treated hypertensive animals body weight gain was reduced after 3, 7 and 14 days, whereas rhIGF-I-treated hypertensive animals continued to gain weight like sham-operated animals. Left ventricular weight and the left, but not the right ventricle/body weight ratio increased more in rhIGF-I- than in vehicle-infused rats. Left ventricular IGF-I mRNA levels remained unchanged after renal clipping in both vehicle- and rhIGF-I-treated rats. However, beta-myosin heavy chain (MHC) mRNA in the left ventricle was 6- to 10-fold increased in clipped controls during the whole postoperative period, and rhIGF-I reduced this increase by more than 50% on days 7 and 14. On the first postoperative day, rhIGF-I prevented the decrease (50%) of alpha-MHC mRNA and the increase (2.5-fold of atrial natriuretic factor mRNA in the left ventricle. Renal clipping did not alter cardiac alpha-actin, but enhanced skeletal alpha-actin mRNA expression in the left ventricle up to 2.5-fold. However, both mRNAs were unaffected by rhIGF-I treatment. Restoration of body weight gain and stimulation of left ventricular cardiac weight by rhIGF-I as well as partial reversion of hypertension-induced changes in cardiac protein expression may reflect beneficial effects contributing to enhance readaptation of the heart to overload.