bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered blood pressure profile, autonomic neuropathy and nephropathy in insulin-dependent diabetic patients
Authors: Monteagudo Patricia T , Nóbrega João C , Cezarini Paulo R , Ferreira Sandra RG , Kohlmann Oswaldo , Ribeiro Artur B , Zanella Maria-Teresa 
Published: December 2008

Monteagudo PT, Nóbrega JC, Cezarini PR, Ferreira SRG, Kohlmann Jr O, Ribeiro AB, Zanella M-T. Altered blood pressure profile, autonomie neuropathy and nephropathy in insulin-dependent diabetic patients. Eur J Endocrinol 1996;135:683–8. ISSN 0809–4643
To evaluate the relationship between autonomie neuropathy (AN) and nephropathy we measured 24-h blood pressure (BP) and overnight urinary albumin excretion (UAE) in 38 patients with insulin dependent diabetes mellitus (IDDM). Autonomie function was evaluated by the heart rate response to deep breathing. Valsalva maneuver, heart rate at rest and BP variation with posture. Sympathetic cutaneous reflex was also tested in both inferior and superior limbs. Patients with mean day diastolic BP (DDBP) ⩽ 90 mmHg without AN (N = 15) compared to 12 normal controls had similar BP values, but compared to those with DDBP ⩽90 mmHg and AN (N = 12) they had lower night diastolic BP (NDBP) (66 ± 4.8 vs 72 ± 8.8 mmHg; p < 0.05) and UAE (9.8 ± 2.3 vs 107.2 ± 3.5 μg/min; p < 0.001). No difference in DDBP was observed between these two diabetic groups (80 ± 3.9 vs 83 ± 6.1 mmHg). Of the 11 patients with DDBP > 90 mmHg, only three were free of AN and only two of the eight with AN where free of diabetic nephropathy. The percentage day/night changes in systolic BP were lower in patients with AN (13 vs 7.9%; p < 0.05) and were inversely related to autonomie score, used as an index of the degree of autonomie dysfunction (r = −0.48; p < 0.01) and to UAE (r = −0.39; p < 0.05). Furthermore, UAE correlated with autonomie score (r = 0.69; p < 0.0001) and with NDBP (r = 0.44; p < 0.01). Our results show that AN in IDDM patients is associated with a reduced nocturnal fall in BP and suggest a pathogenic role of autonomie dysfunction in the development of diabetic nephropathy, possibly favoring both BP elevation during the night and increases in intraglomerular pressure.
Maria Teresa Zanella, Disciplina de Endocrinologia, Escola Paulista de Medicina, Rua Botucatu 720, Vila dementino, São Paulo, Brazil
Do insulin-like growth factor binding proteins (IGFBPs) modulate the IGF-I growth promoting and differentiating effects in human neuroblastoma cells?
Authors: Cianfarani Stefano , Germani Daniela , Rossi Paola , Spagnoli Anna , Mercanti Delio 
Published: December 2008

Cianfarani S, Germani D, Rossi P, Spagnoli A, Mercanti D. Do insulin-like growth factor binding proteins (IGFBPs) modulate the IGF-I growth promoting and differentiating effects in human neuroblastoma cells? Eur J Endocrinol 1996;135:716–23. ISSN 0804–4643
The insulin-like growth factors (IGFs) are known to stimulate both the proliferation and differentiation of neuroblastoma cells, but the role of the IGF binding proteins (IGFBPs) has not yet been established. In this study, human neuroblastoma SH-SY5Y cells have been treated with IGF-I and its potent analogue des (1–3) IGF-I alone or following preincubation with a differentiating agent such as 12-o-tetradecanoylphorbol-13-acetate (TPA). Cell proliferation and differentiation were evaluated. Conditioned medium was tested for the presence of IGFBPs by ligand blotting. The SH-SY5Y cell proliferation was maximally stimulated by des (1–3) IGF-I. The TPA-induced differentiation of SH-SY5Y, evaluated by assessment of cell morphology and GAP-43 expression as a biochemical marker of differentiation, was potentiated by nanomolar concentrations of des (1–3) IGF-I and, to a smaller extent, IGF-I. Conditioned medium showed the presence of a major IGFBP band with an approximate molecular weight of 32.5 kD and a very faint band of approximately 24 kD. The IGFBP immunoblotting results suggest that the predominant band might represent IGFBP-2. Our data represent a first demonstration of the presence of IGFBPs in conditioned medium of human neuroblastoma SH-SY5Y cells. The finding that the potent IGF-I analogue des (1–3) IGF-I with reduced affinity for IGFBPs induce major effects on cell growth and differentiation suggests that the IGFBPs may play an active role in the neuronal response to the proliferative and differentiative effects of IGF-I.
Stefano Cianfarani, Laboratory of Paediatric Endocrinology, Department of Paediatrics, "Tor Vergata" University, via di Tor Vergata 135, 00133 Rome, Italy
Infrequent mutations of p16INK4A and p15INK4B genes in human pituitary adenomas
Authors: Yoshimoto Katsuhiko , Tanaka Chisato , Yamada Shozo , Kimura Takehiko , Iwahana Hiroyuki , Sano Toshiaki , Itakura Mitsuo 
Published: December 2008

Abstract
The p16INK4A and p15INK4B genes on chromosome 9p21 encode the p16 and p15 inhibitors of cyclin D/cyclin-dependent kinase 4 complexes respectively. Mutations and deletions of the p16INK4A gene have been found in melanomas and many other types of tumors. To assess the role of the p16INK4A and p15INK4B genes in tumorigenesis of the pituitary gland, 31 sporadic pituitary adenomas and 2 pituitary adenomas in familial acrogigantism were examined for loss of heterozygosity on 9p21–22 and screened for mutations in the p16INK4A and p15INK4B genes. To identify pituitary adenomas which had lost which had lost 9p21–22, pituitary adenomas were genotyped with markers flanking the p16INK4A and p15INK4B loci. The frequency of mutations in coding regions of the p16INK4A and the p15INK4B genes in pituitary adenomas was determined with polymerase chain reation-single strand conformation polymorphism analysis and sequencing of variants. Of the 33 pituitary adenomas, two revealed loss of 9p21–22 sequences, but none of them had tumor-specific mutations. We conclude that mutations of the p16INK4A and p15INK4B genes are not required for tumorigenesis of the pituitary gland.
European Journal of Endocrinology 136 74–80
The stimulatory effect of endothelin-1 on regenerating adrenal cortex is reversed by nifedipine
Authors: Zieleniewski Wojciech 
Published: December 2008

Abstract
Endothelin-1 (ET-1), a potent vasoconstrictor, was found to act in non-vascular tissues, for example it enhanced aldosterone output from adrenal zona glomerulosa. As the adrenal cortex is capable of regeneration after enucleation, it seemed of interest to study the effects of ET-1 on adrenocortical regeneration. The study was performed on adult rats subjected to left adrenal enucleation combined with contralateral adrenalectomy. Mitotic index was employed to assess the proliferation of regenerating adrenal cortex cells. Plasma corticosterone was measured by a standard RIA kit. ET-1 significantly raised the mitotic index of regenerating rat adrenal cortex by six days after surgery. On the other hand, nifedipine reduced the proliferation ratio and abolished the stimulatory influence of ET-1. Similarly, ET-1 enhanced corticosterone output from the regenerating adrenal cortex, and this could be prevented by the addition of nifedipine.
This study has shown that ET-1 might act as a regulatory factor on the regenerating adrenal cortex via calcium channels.
European Journal of Endocrinology 136 121–122
True hermaphroditism: clinical aspects and molecular studies in 16 cases
Authors: Damiani Durval , Fellous Marc , McElreavey Ken , Barbaux Sandrine , Barreto Elenilde S A , Dichtchekenian Vaê , Setian Nuvarte 
Published: December 2008

Abstract
Although true hermaphroditism (TH) accounts for less than 10% of intersex patients, it stands as a diagnostic challenge and has allowed a better understanding of the mechanisms involved in sexual differentiation. In this paper we review the clinical and laboratory data as well as molecular biology findings on 16 TH patients followed up at the Pediatric Endocrine Unit, Instituto da Criança, Hospital das Clínicas, São Paulo University Medical School. They were of a mean age of 3 years 8 months and nine of them were black. All the patients had ambiguous external genitalia as the main complaint. The 46,XX karyotype accounted for 50% of the cases and the ovotestis was the most frequent gonad found (59%). In the eight TH patients with a 46,XX karyotype, the sex-determining region of the Y chromosome (SRY) was negative, posing an intriguing question about the testicular differentiation mechanisms involved in these cases. In 7/19 ovotestes, the ovarian portion of the gonad has been preserved, keeping open the possibility of fertility. The female sex option was made in 10/16 cases (62·5%) and three patients exhibited spontaneous puberty. The mechanism through which testicular tissue develops without SRY has not yet been completely clarified, suggesting the involvement of the X chromosome as well as autosomal genes in the process.
European Journal of Endocrinology 136 201–204
Mechanism of angiotensin II-induced arachidonic acid metabolite release in aortic smooth muscle cells: involvement of phospholipase D
Authors: Shinoda Junji , Kozawa Osamu , Suzuki Atsushi , Watanabe-Tomita Yasuko , Oiso Yutaka , Uematsu Toshihiko 
Published: December 2008

Abstract
In a previous study, we have shown that angiotensin II (Ang II) activates phosphatidylcholinehydrolyzing phospholipase D due to Ang II-induced Ca2+ influx from extracellular space in subcultured rat aortic smooth muscle cells. In the present study, we have investigated the role of phospholipase D in Ang II-induced arachidonic acid (AA) metabolite release and prostacyclin synthesis in subcultured rat aortic smooth muscle cells. Ang II significantly stimulated AA metabolite release in a concentration-dependent manner in the range between 1 nmol/l and 0·1 μmol/l. d,l-Propranolol hydrochloride (propranolol), an inhibitor of phosphatidic acid phosphohydrolase, significantly inhibited the Ang II-induced release of AA metabolites. The Ang II-induced AA metabolite release was reduced by chelating extracellular Ca2+ with EGTA. Genistein, an inhibitor of protein tyrosine kinases, significantly suppressed the Ang II-induced AA metabolite release. 1,6-Bis-(cyclohexyloximinocarbonylamino)-hexane (RHC-80267), a potent and selective inhibitor of diacylglycerol lipase, significantly inhibited the Ang II-induced AA metabolite release. Both propranolol and RHC-80267 inhibited the Ang II-induced synthesis of 6-keto-prostaglandin F1α, a stable metabolite of prostacyclin. The synthesis was suppressed by genistein. These results strongly suggest that the AA metabolite release induced by Ang II is mediated, at least in part, through phosphatidylcholine hydrolysis by phospholipase D activation in aortic smooth muscle cells.
European Journal of Endocrinology 136 207–212
Influence of prolonged fasting and thyroid hormone on the α2-adrenergic response in isolated epididymal adipocytes of Wistar rats
Authors: Cheikh Rajae Ben , Chomard Philippe , Beltramo Jean Luc , Autissier Nicole , Dumas Paul 
Published: December 2008

Abstract
Fasting and thyroid hormone have been reported to modulate the β-adrenergic pathway of lipolysis in rat, but their effects on the α2-adrenergic response are not well known. The purpose of the present study was to investigate this point. Male Wistar rats, 3 weeks old, were thyroidectomized surgically, kept for 1 month at 25 °C and then fasted or not fasted for 3 days with or without daily intraperitoneal injection of 3,5,3′-tri-iodo-l-thyroni(T3; 4·6 nmol/100 g body weight). Age-matched, sham-operated, fed and fasted euthyroid rats were used as controls. The experiments were carried out using isolated epididymal adipocytes. The α2-adrenergic agonist UK 14304 (UK) inhibited the stimulated lipolysis more in fed than in fasted euthyroid rats whereas it had no effect in hypothyroid or T3-treated hypothyroid rats. The α2-adrenergic antagonist idazoxan reversed the antilipolytic effect of UK more in fasted than in fed euthyroid rats. The α2-adrenergic antagonist RX 82 1002 (RX) did so, but at lower concentrations than those of idazoxan. Idazoxan slightly increased the glycerol release in hypothyroid and especialiy T3-treated hypothyroid rats. RX had practically no effect on the production of glycerol in these animals. The findings suggest that (a) fasting and probably hypothyroidism decrease the α2-adrenergic response in adipocytes from rats, (b) T3 treatment of hypothyroid rats has no effect on the α2 response, and (c) thyroid hormone does not directly modulate the α2-adrenergic response in rat adipocytes.
European Journal of Endocrinology 136 223–229
Decreased serum IGF-I and dehydroepiandrosterone sulphate may be risk factors for the development of reduced bone mass in postmenopausal women with endogenous subclinical hyperthyroidism
Authors: Földes János , Lakatos Péter , Zsadányi Júlia , Horváth Csaba 
Published: December 2008

Abstract
Postmenopausal women with endogenous subclinical hyperthyroidism seem to have reduced bone mass, which does not correlate with serum thyroid hormone levels. Relative insufficiencies of IGF-I and dehydroepiandrosterone sulphate (DHEAS) might be additional risk factors for low bone density in these patients. We measured IGF-I, IGF-binding protein-3 (IGFBP-3) and DHEAS levels together with bone mineral density (BMD) of the femoral neck and lumbar spine in women with an autonomously functioning thyroid nodule. Sixty-three women were classified as subclinical hyperthyroid (31 pre- and 32 postmenopausal) and 39 as overt hyperthyroid (16 pre- and 23 postmenopausal) and results were compared with data obtained from 41 age-matched euthyroid healthy women. In premenopausal women BMD was reduced only in the overt hyperthyroid group, and only in the spine, to 92% (P < 0·05). Serum IGF-I as well as IGFBP-3 were increased in the manifest hyperthyroid group, to 157% (P < 0·001) and 129% (P < 0·05) respectively, whereas DHEAS levels did not change in either premenopausal patient group. In postmenopausal women BMD was significantly reduced both in the subclinical hyperthyroid group (spine to 90% and femoral neck to 88%; P < 0·05), as well as in the hyperthyroid group (spine to 78% and femoral neck to 86%; P < 0·01). In contrast to premenopausal women, serum IGF-I and IGFBP-3 did not change in the two groups who were postmenopausal and serum DHEAS levels were reduced to 58% (P < 0·001) in both postmenopausal groups with subclinical as well as overt hyperthyroidism. In the same two groups of patients, serum IGF-I and DHEAS levels correlated with BMD (femoral neck; both r = 0·50, P < 0·05). In conclusion, women with a solitary autonomous thyroid nodule with subclinical hyperthyroidism have reduced BMD only if they are postmenopausal. This is probably due to the effect of subtle increases in thyroid hormone production together with lack of oestrogen protection of the skeleton. But additional risk factors for the development of enhanced bone loss might be a state of relative IGF-I and DHEAS insufficiency in these patients as well as in postmenopausal women with overt hyperthyroidism.
European Journal of Endocrinology 136 277–281
Trimethoprim/sulfamethoxazole-induced hypoglycemia in a malnourished patient with severe infection
Authors: Hekimsoy Zeliha , Biberoǧlu Sevinç , Çömlekçi Abdurrahman , Tarhan Oktay , Mermut Cem , Biberoǧlu Kadir 
Published: December 2008

Abstract
Hypoglycemia resulting from the combination of sulfonylurea and sulfonamides is a recognized drug interaction. Hypoglycemia induced by sulfonamides alone may be encountered less frequently. Because of their structural similarities to sulfonylureas. sulfonamides are liable to facilitate hypoglycemia by increasing insulin release in susceptible individuals. Sulfonamides can potentiate the hypoglycemic effect of sulfonylurea agents when given in combination. We describe a malnourished patient with severe infection who developed hypoglycemia during high-dose trimethoprim/sulfamethoxazole therapy. Elevated C-peptide concentrations during the hypoglycemic episode indicate that hypoglycemia resulted from increased endogenous insulin secretion. As malnourished patients are prone to hypoglycemia, we suggest that they should be monitored carefully if they are on sulfonamide therapy.
European Journal of Endocrinology 136 304—306
Extrarenal aspects of angiotensin II function
Authors: Csikós Tamás , Gallinat Stefan , Unger Thomas 
Published: December 2008

Abstract
The cloning of angiotensin II (Ang II) receptor genes and the availability of specific receptor ligands allows characterization of Ang II receptor-mediated actions. Most of the well-known Ang II effects such as vasoconstriction, drinking response and cell proliferation are mediated through the AT1 receptor. Little is known about the physiological effect of the AT2 receptor, though there are some reports describing the involvement of the AT2 receptor in blood pressure regulation. Recent data demonstrate that the AT2-mediated actions are inhibitory to AT1- and mitogen-induced growth effects, indicating a balancing mechanism for Ang II-controlled mechanisms. It has also been demonstrated that AT2 receptor inactivation induces endothelial cell proliferation in the presence of Ang II. Additionally, AT2 receptor activation enhances nerve growth factor-induced differentiation of PC12W cells and a role in apoptotic changes has also been reported.
Based on recent findings, this article focuses on the role of Ang II in growth and differentiation processes with respect to the AT2 receptor in these events.
European Journal of Endocrinology 136 349–358
Molecular analysis of the RET proto-oncogene in patients with sporadic medullary thyroid carcinoma: a novel point mutation in the extracellular cysteine-rich domain
Authors: Bugalho Maria João , Frade João Pedro , Santos Jorge Rosa , Limbert Edward , Sobrinho Luis 
Published: December 2008

Abstract
Germline point mutations in the RET proto-oncogene are associated with multiple endocrine neoplasia type 2 (2A and 2B) and familial medullary thyroid carcinoma. On the other hand, somatic point mutations of RET have been described in a subset of sporadic medullary thyroid carcinomas (MTCs).
We examined tumor and blood DNA of thirteen apparently sporadic MTC patients for mutations in RET exons 10, 11, 13, 15 and 16 to determine whether they had true sporadic tumors or either de novo or occult germline mutations.
Three different somatic missense mutations were documented in seven patients. In five patients a mutation in exon 16, codon 918, (ATG→ACG) causing a Met→Thr substitution was found. In the remaining two patients the mutation affected exon 11: codon 630 in one case and codon 634 in the other. In both cases a T→C transversion was identified causing a Cys→Arg substitution.
In conclusion, absence of a germline mutation in RETexons 10, 11, 13 or 16 is evidence against an inherited form in all cases. In seven patients, identification of a somatic mutation supported the previous clinical diagnosis of sporadic medullary thyroid carcinoma; in one of them we identified a hitherto undescribed somatic point mutation at codon 630.
European Journal of Endocrinology 136 42 3–426
Improvement of cytochrome P450c17 catalytic processivity as a novel mechanism to attenuate hormonal consequences of enzyme decay in the testes after a gonadotropin surge
Authors: Kühn-Velten W Nikolaus 
Published: December 2008

Abstract
Objective: The aim of this study was to gain understanding of the apparent discrepancy between the moderate restriction of testosterone synthesizing capacity and the nearly complete decay of the androgen-producing enzyme, cytochrome P450c17 (CYP17; steroid 17α-hydroxylase/17,20-lyase), in rat testes during the desensitization phase induced by a single, high-dose gonadotropin (human chorionic gonadotropin, hCG) injection.
Design and methods: Adult male rats received 25IU hCG i.v., and purified Leydig cells and crude interstitial cell microsomes were prepared 0, 4, 12, 24, 48, 72, 120 and 192 h afterwards. Component CYP17 activities, i.e. simultaneously catalyzed productive androgen formation and abortive 17α-hydroxyprogesterone release, and their ratio (processivity), were compared with CYP17 levels and testosterone secretion rates.
Results: Leydig cells isolated 48 h after the artificial hCG surge produce 62% less testosterone than control cells upon stimulation in vitro, though CYP17 levels are reduced by 97%. Its total activity decreases by 87%, resulting in a 4·5-fold rise in the turnover number; the processivity is additionally improved 5-fold over controls. Parallel changes occur in interstitial cell microsomes; a negative linear correlation exists between the ratio of productive over total CYP17 activities and the actual CYP17 concentrations. CYP17 is partly denatured to P420 during hCG action, but other heme proteins (cytochrome b5) remain unchanged. Animal treatment with estradiol results in CYP17 downregulation without any concomitant effect on enzyme processivity.
Conclusion: Improved CYP17 processivity is suggested to be the consequence of (otherwise ratelimiting) improved electron transfer efficiency towards CYP17. It explains the relatively high testosterone secretion during Leydig cell desensitization and is interpreted to be a protective mechanism to confine adverse consequences of enzyme decay.
European Journal of Endocrinology 136 438–443
The revised 8307 base pair coding sequence of human thyroglobulin transiently expressed in eukaryotic cells
Authors: van de Graaf Simone A R , Pauws Erwin , de Vijlder Jan J M , Ris-Stalpers Carrie 
Published: December 2008

Abstract
We developed a transient transfection system for human thyroglobulin (TG) cDNA in both human thyroid cells and in COS-1 cells.
Four overlapping TG cDNA fragments were amplified by reverse transcription-PCR from RNA of normal thyroid tissue. The most 5′ fragment includes the natural translation initiation site and the sequence encoding the signal peptide (SP). After subcloning, the nucleotide sequence was determined and compared with the published human sequence, resulting in the detection of 30 nucleotide variations. For validation purposes, all variations were screened in 6–12 normal human alleles. Twenty-one were present in all screened alleles and have to be revised in the published nucleotide sequence. Since one variation concerns a triplet insertion, the coding sequence of the mature human thyroglobulin is 8307 nucleotides encoding 2750 amino acids.
The TG cDNA constructs were transiently transfected in HTori 3 and COS-1 cells and protein expression was detected using a polyclonal anti-human-TG on fixed cells and after SDS-PAGE. In both cell-lines all four TG protein fragments were expressed. The mannose structures detected on the proteins by lectins and localization after expression in the cells suggest that only the N-terminal TG fragment (containing the SP) is directed to the endoplasmatic reticulum but is unable to reach the Golgi complex.
The described expression system in human thyrocytes will be a helpful tool in studying the structure–function relationship of human TG in thyroid hormonogenesis.
European Journal of Endocrinology 136 508–515