bluuebunny/crossref_metadata_2025_split huggingface dataset:
Midnight serum cortisol as a marker of increased cardiovascular risk in patients with a clinically inapparent adrenal adenoma
Authors: Terzolo Massimo , Bovio Silvia , Pia Anna , Conton Pier Antonio , Reimondo Giuseppe , Dall’Asta Chiara , Bemporad Donatella , Angeli Alberto , Opocher Giuseppe , Mannelli Massimo , Ambrosi Bruno , Mantero Franco 
Published: August 2005

Objective: There is scant information on the morbidity associated with subclinical Cushing’s syndrome in patients with a clinically inapparent adrenal adenoma. In the present study, we have determined the prevalence of alterations of the hypothalamic–pituitary–adrenal axis in such patients and examined whether any correlation between endocrine data and the clinical phenotype exists.
Design and methods: A multi-institutional retrospective study was carried out on 210 patients (135 women and 75 men aged 19–81 years) with an adrenal adenoma detected serendipitously between 1996 and 2000 in four referral centers in Italy.
Results: Hypertension was observed in 53.8%, obesity in 21.4% and hyperglycemia in 22.4% of patients. The 47 patients with midnight serum cortisol >5.4 μg/dl, a value corresponding to the 97th centile of 100 controls, were older and displayed greater fasting glucose (120.4±52.2 mg/dl vs 105.1±39.2 mg/dl, P = 0.04) and systolic blood pressure (148.3±14.6 mmHg vs 136.4±16.2 mmHg, P = 0.0009) than the 113 patients with normal cortisol levels. The difference in systolic blood pressure remained statistically significant (P = 0.009) when age was used as a covariate. The percentage of hypertensive patients undergoing treatment was not different between the two groups (90.5 and 97.1%) but the percentage of patients with controlled hypertension was significantly lower among the hypercortisolemic patients (12.5 vs 32.4%, P = 0.04). Glycated haemoglobin (HbA1c) levels were higher in the hypercortisolemic diabetic patients (8.9±1.1% vs 7.1±1.3%, P = 0.005).
Conclusions: Elevated midnight cortisol concentration is a reliable test to select a subgroup of patients with a clinically inapparent adrenal adenoma with an adverse cardiovascular risk profile.
Relationship between leptin, insulin, body composition and liver steatosis in non-diabetic moderate drinkers with normal transaminase levels
Authors: Valtueña Silvia , Numeroso Filippo , Ardigò Diego , Pedrazzoni Mario , Franzini Laura , Piatti Pier Marco , Monti Lucilla , Zavaroni Ivana 
Published: August 2005

Objective: Obesity and insulin resistance play a major role in the development of liver steatosis (LS), but also relative leptin resistance has been reported to correlate with LS in humans. Our objective was to investigate the relationship between serum leptin, insulin, obesity and LS in non-diabetic males (n = 74) and postmenopausal females (n = 50) with normal transaminase levels and low-to-moderate alcohol intake.
Methods: A medical history to retrieve information about health status, current medications, alcohol consumption and history of viral or toxic hepatitis; a physical examination including height, weight, waist circumference and blood pressure; a fasting blood draw for the determination of glucose, insulin, leptin, lipid profile, transaminases and uric acid; an oral glucose tolerance test to exclude type 2 diabetes; a dual-energy X-ray absorptiometry scan to assess fat mass (FM) and lean body mass (LBM), and an echography of the liver to assess LS.
Results: Fasting leptin and insulin were highly correlated with FM in men (R = 0.767 and R = 0.495 respectively, P < 0.001) and women (R = 0.713 and R = 0.526 respectively, P < 0.001). After correction for FM, leptin showed a significant negative correlation with LBM in men (R = −0.240, P = 0.039), but not in women (R = −0.214, P = 0.132). The positive relationship observed between leptin, insulin and LS persisted after adjustment of leptin and insulin for body composition only in men (R = 0.415, P < 0.001 and R = 0.339, P = 0.003 respectively for leptin and insulin vs LS). Adjusted means (95% confidence intervals) of leptin increased significantly across categories of LS in men even when insulin was considered in the model (absent = 7.1 ng/ml (5.6–8.5), mild = 8.2 ng/ml (7.2–9.2), moderate/severe = 12.1 ng/ml (10.3–14.0); P < 0.001), whereas no significant relationship was observed between insulin and LS after leptin was accounted for.
Conclusion: Serum concentrations of leptin and insulin are positively correlated in men independently of body composition, but not in postmenopausal women. In men, the steatogenic effect of hyperinsulinemia/insulin resistance in the context of low-to-moderate alcohol consumption appears to be mediated by high concentrations of serum leptin, whereas body fat alone could identify postmenopausal women at high risk for LS.
Pit-1 is expressed in normal and tumorous human breast and regulates GH secretion and cell proliferation
Authors: Gil-Puig C , Seoane S , Blanco M , Macia M , Garcia-Caballero T , Segura C , Perez-Fernandez R 
Published: August 2005

Background: The transcription factor pituitary-1 (Pit-1) is mainly expressed in the pituitary gland, where it has critical roles in cell differentiation and as a transcriptional factor for GH and prolactin (PRL). It is also expressed in human extrapituitary tissues (placenta, lymphoid and haematopoietic tissues) and cell lines (human breast adenocarcinoma cells, MCF-7). Despite the widely suggested roles of GH and PRL in the progression of proliferative mammary disorders, Pit-1 expression in human mammary gland has not yet been reported.Objective: To evaluate the expression of Pit-1 in human breast and, using the MCF-7 cell line, to investigate whether Pit-1 overexpression regulates GH expression and increases cell proliferation.Methods: Using real-time RT-PCR, western blotting and immunohistochemistry, we evaluated the expression of Pit-1 mRNA and protein in seven normal human breasts and 14 invasive ductal mammary carcinomas. GH regulation by Pit-1 in MCF-7 cells was evaluated using RT-PCR, western blotting, ELISA and transfection assays. Cell proliferation was evaluated using bromodeoxyuridine.Results: We found expression of Pit-1 mRNA and protein in both normal and tumorous human breast. We also found that Pit-1 mRNA levels were significantly increased in breast carcinoma compared with normal breast. In MCF-7 cells, Pit-1 overexpression increased GH mRNA and protein concentrations and significantly increased cell proliferation.Conclusions: These findings indicate that Pit-1 is expressed in human breast, that it regulates endogenous human mammary GH secretion, and that it increases cell proliferation. This suggests that, depending on its level of expression, Pit-1 may be involved in normal mammary development, breast disorders, or both.
Resistin levels in hyperthyroid patients before and after restoration of thyroid function: relationship with body weight and body composition
Authors: Krassas Gerasimos E , Pontikides Nikolaos , Loustis Kostas , Koliakos Georgios , Constantinidis Theodoros , Panidis Dimitrios 
Published: August 2005

Background: Resistin is a recently discovered peptide hormone that belongs to a family of tissue-specific resistin-like molecules. To date, very few studies have reported on resistin concentrations in hyperthyroid patients, and they present controversial results.
Objectives: To undertake a controlled, prospective study to investigate resistin concentrations in hyperthyroidism before and after restoration of euthyroidism and to correlate the results with body weight, body fat, waist circumference and body mass index (BMI).
Patients and Methods: A total of 43 hyperthyroid patients (12 men and 31 women) were investigated, in addition to 23 controls. Anthropometric parameters and resistin concentrations were measured. All the patients commenced taking antithyroid drugs and 3–4 months later the same investigations were performed in 36 of the 43 individuals.
Results: Hyperthyroid patients exhibited increased resistin concentrations in comparison with controls. Normalization of thyroid hormones was accompanied by a significant decrease in resistin concentration. A sex difference was also found, men showing a significant decrease in resistin concentrations, whereas in women no such difference was found. Resistin concentrations did not correlate with different anthropometric parameters, age and thyroid hormones, either before or after treatment.
Conclusions: This study demonstrates for the first time that, although resistin concentrations are increased in hyperthyroidism, they are not associated with body weight, body fat, waist circumference or BMI, which makes it unlikely that resistin plays a crucial part in thermogenesis and energy homeostasis in thyrotoxic patients.
The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index
Authors: Corneli Ginevra , Di Somma Carolina , Baldelli Roberto , Rovere Silvia , Gasco Valentina , Croce Chiara Giulia , Grottoli Silvia , Maccario Mauro , Colao Annamaria , Lombardi Gaetano , Ghigo Ezio , Camanni Franco , Aimaretti Gianluca 
Published: August 2005

Objective: The diagnosis of growth hormone (GH) deficiency (GHD) in adults is based on a reduced peak GH response to provocative tests, such as the insulin tolerance test (ITT) and the GH-releasing hormone-arginine (GHRH-ARG) test. However, the cut-off limits of peak GH response in lean subjects are not reliable in obese patients; this is noteworthy since adult GHD is often associated with obesity. Aim of this study was to evaluate the diagnostic cut-off limits of peak GH response to the GHRH-ARG test in overweight and obese as well as in lean population.
Design and methods: The GH responses to the GHRH-ARG test were studied in 322 patients with organic hypothalamic-pituitary disease and in 318 control subjects. Patients were subdivided into two groups on the basis of the number of pituitary hormone deficits, except for GH deficiency: (a) patients with total pituitary hormone deficit (TPHD) and (b) patients without or with no more than two pituitary hormone deficits (PHD). Both patients and control subjects were divided into three subgroups according to body mass index (BMI): lean (BMI <25 kg/m2), overweight (BMI ≥25 and <30 kg/m2) and obese (BMI ≥30 kg/m2). TPHD patients were assumed to be GH deficient, whereas PHD patients may include subjects with either normal or impaired GH secretion. The statistical analysis was carried out by the Receiver-Operating Characteristic curve analysis (Medcalc 7.2). The diagnostic cut-off points were calculated for lean, overweight and obese subjects to provide optimal separation of GH-deficient patients and control subjects according to two criteria: (1) a balance between high sensitivity and high specificity; (2) to provide the highest pair of sensitivity/specificity values for GH deficiency.
Results: In the lean population the best pair of values, with highest sensitivity as 98.7% and highest specificity as 83.7%, was found using a peak GH cut-off point of 11.5 μg/l. In the overweight population the best pair of values, 96.7 and 75.5%, respectively, was found using a peak GH cut-off point of 8.0 μg/l. In the obese population the best pair of values, 93.5 and 78.3%, respectively, was found using a peak GH cut-off point of 4.2 μg/l. Applying the above mentioned cut-off points, among PHD patients we found that 80 subjects (72%) were GHD whereas 31 (28%) had normal GH secretion.
Conclusions: In conclusion the GHRH-ARG test is a reliable tool for the diagnosis of adult GH deficiency in lean, overweight and obese patients, provided that specific BMI-related cut-off limits are assumed.
Predictors and rates of treatment-resistant tumor growth in acromegaly
Authors: Besser G M , Burman P , Daly A F 
Published: August 2005

Background: Multimodal therapy for acromegaly affords adequate disease control for many patients; however, there remains a subset of individuals that exhibit treatment-resistant disease. The issue of treatment-resistant pituitary tumor growth remains relatively under-explored.
Methods: We assessed the literature for relevant data regarding the surgical, medical and radiotherapeutic treatment of acromegaly in order to identify the factors that were predictive of aggressive or treatment-resistant pituitary tumor behavior in acromegaly and undertook an assessment of the rates of failure to control tumor progression with available treatment modalities.
Results: Young age at diagnosis, large tumor size, high growth hormone secretion and certain histological markers are predictors of future aggressive tumor behavior in acromegaly. Significant tumor regrowth occurs in less than 10% of cases thought to be cured surgically, whereas failure to control tumor growth is seen in less than 1% of patients receiving radiotherapy. Somatostatin analogs induce a variable degree of tumor shrinkage in acromegaly but up to 2.2% of somatostatin analog-treated tumors continue to grow. Relative to other therapies, limited data are available for pegvisomant, but these indicate that persistent tumor growth occurs in 1.6–2.9% of cases followed up regularly with serial magnetic resonance imaging scans.
Conclusions: Treatment-resistant tumor progression occurs in a small minority of patients with acromegaly, regardless of treatment modality. Young patients with large tumors or those with high pre-treatment levels of growth hormone particularly warrant close monitoring for continued tumor progression during treatment for acromegaly.
Transsphenoidal surgery in acromegaly investigated by intraoperative high-field magnetic resonance imaging
Authors: Fahlbusch Rudolf , Keller Boris v , Ganslandt Oliver , Kreutzer Jürgen , Nimsky Christopher 
Published: August 2005

Objective: The aim of the study was to evaluate the effect of intraoperative high-field (1.5 Tesla) magnetic resonance imaging (MRI) on the results of transsphenoidal surgery of GH-secreting pituitary macroadenomas.
Methods: Twenty-three acromegalic patients (mean tumor size, 25 ± 12 mm; untreated preoperative GH, 4.2–159 μg/l; IGF-I, 349–1111 μg/l) were investigated by intraoperative high-field MRI. If intraoperative imaging depicted an accessible tumor remnant, resection was continued.
Results: In five patients intraoperative MRI led to further tumor removal, two of these met the consensus criteria for endocrine remission after 3 months. In two patients basal GH and oral glucose tolerance test (OGTT) were <2 μg/l, only IGF-I was slightly elevated, and in one patient GH was <5 μg/l and OGTT was 2 μg/l, with elevated IGF-I. Final intraoperative MRI showed no tumor remnants in 14 patients; eight of them met the consensus criteria for remission of acromegaly. In the patients with MRI showing incomplete removal (four suspect findings and five patients with intended partial removal) none was normalized.
Conclusion: With regard to the patients with a tumor configuration in whom complete tumor removal was considered (n = 18), intraoperative MRI increased the rate of endocrine normalization from 33 to 44% applying the consensus criteria, and improved endocrine outcome to ‘nearly normalization’ in another 17%. With regard to preoperative GH levels and tumor size, intraoperative MRI can help to achieve endocrine remission in patients who are normally considered not to be curable. However, taking GH as the tumor marker, even intraoperative high-field MRI was not able to detect tumor remnants in every case.
Tissue Persistence and Vaccine Efficacy of an O Polysaccharide Mutant Strain of Edwardsiella ictaluri
Authors: Lawrence Mark L. , Banes Michelle M. 
Published: August 2005

Abstract
Studies were conducted to determine the tissue persistence and vaccine efficacy of a previously constructed isogenic O polysaccharide (OPS) mutant strain (93–146 R6) of the bacterium Edwardsiella ictaluri in channel catfish Ictalurus punctatus. The OPS-negative strain retained the ability to infect channel catfish following immersion exposure and persisted in the trunk kidney at least 14 d, whereas previously reported attenuated E. ictaluri strains were cleared by 72 h postexposure. Vaccination with 93–146 R6 by intraperitoneal injection provided significant protection against subsequent immersion challenge with the virulent parental strain, but vaccination by immersion did not provide protection. The commercial vaccine RE-33 provided significant protection when fish were vaccinated by immersion, but RE-33 was more virulent than 93–146 R6 when given by intraperitoneal injection.
Differentiation and Characterization of Myeloid Cells
Authors: Gaines Peter , Berliner Nancy 
Published: August 2005

AbstractRecent molecular studies of myeloid differentiation have utilized several in vitro models of myelopoiesis. Hematopoietic progenitors expressing the CD34+ antigen can be induced in vitro in a process that recapitulates the normal myeloid development. Two human leukemic cell lines, NB‐4 and HL‐60, have been demonstrated to undergo retinoic acid–induced myeloid development, however, both cell lines exhibit defects in the upregulation of late‐expressed neutrophil‐specific genes. In contrast, two murine factor–dependent cell models of myelopoiesis express the full range of neutrophil maturation markers: 32Dcl3 cells, which undergo G‐CSF‐induced myeloid maturation, and EML/EPRO cells, which develop into mature neutrophils in response to cytokines and retinoic acid. In this unit, the induction of myeloid maturation in each of these model systems is described. Commonly used techniques to test for myeloid characteristics of developing cells are also described. Together, these assays provide a solid foundation for in vitro investigations of myeloid development.
Analysis of Protein Transport to Lysosomes
Authors: Schaub Beat E. , Nair Prashant , Rohrer Jack 
Published: August 2005

AbstractLysosomes are terminal degradative organelles that are found in all higher eukaryotic cells. The biogenesis of lysosomes involves the transport of various acid hydrolases and transmembrane glycoproteins from their site of synthesis in the endoplasmic reticulum through the biosynthetic and endocytic pathways. Protein transport to lysosomes can be studied by a combination of techniques based on the separation of intracellular organelles. Percoll density gradient centrifugation has long been the method of choice for separating lysosomes from other organelles in cell homogenates, and accordingly, this unit describes protocols for obtaining reasonably pure lysosomal fractions from mammalian cells using Percoll density gradient separation.
Modular materials by self‐assembly
Authors: Tirrell Matthew 
Published: August 2005

AbstractSelf‐assembly is a promising route to producing materials and other chemical products with unprecedented functionality for biomedical, electronic, catalytic and separation process technologies. However, self‐assembly will not achieve its full potential unless it is taken seriously as a manufacturing process, as opposed to a laboratory technique, and the obstacles to large‐scale implementation are tackled and surmounted. This article, which is an extension of an earlier AIChE Journal Perspectives article, defines and suggests important research directions for chemical engineers in an effort to develop self‐assembly into a practical process technology. © 2005 American Institute of Chemical Engineers AIChE J, 2005
Chromosome rearrangements in Cornelia de Lange syndrome (CdLS): Report of a der(3)t(3;12)(p25.3;p13.3) in two half sibs with features of CdLS and review of reported CdLS cases with chromosome rearrangements
Authors: DeScipio Cheryl , Kaur Maninder , Yaeger Dinah , Innis Jeffrey W. , Spinner Nancy B. , Jackson Laird G. , Krantz Ian D. 
Published: August 2005

AbstractCornelia de Lange syndrome (CdLS; OMIM 122470) is a dominantly inherited disorder characterized by multisystem involvement, cognitive delay, limb defects, and characteristic facial features. Recently, mutations in NIPBL have been found in ∼50% of individuals with CdLS. Numerous chromosomal rearrangements have been reported in individuals with CdLS. These rearrangements may be causative of a CdLS phenotype, result in a phenocopy, or be unrelated to the observed phenotype. We describe two half siblings with a der(3)t(3;12)(p25.3;p13.3) chromosomal rearrangement, clinical features resembling CdLS, and phenotypic overlap with the del(3)(p25) phenotype. Region‐specific BAC probes were used to fine‐map the breakpoint region by fluorescence in situ hybridization (FISH). FISH analysis places the chromosome 3 breakpoint distal to RP11‐115G3 on 3p25.3; the chromosome 12 breakpoint is distal to BAC RP11‐88D16 on 12p13.3. A review of published cases of terminal 3p deletions and terminal 12p duplications indicates that the findings in these siblings are consistent with the del(3)(p25) phenotype. Given the phenotypic overlap with CdLS, we have reviewed the reported cases of chromosomal rearrangements involved in CdLS to better elucidate other potential loci that could harbor additional CdLS genes. Additionally, to identify chromosome rearrangements, genome‐wide array comparative genomic hybridization (CGH) was performed on eight individuals with typical CdLS and without identifiable deletion or mutation of NIPBL. No pathologic rearrangements were identified. © 2005 Wiley‐Liss, Inc.
Contribution to the Qualification of Technical Microwave Systems and to the Validation of Microwave‐Assisted Reactions and Processes
Authors: Nüchter M. , Ondruschka B. , Weiß D. , Beckert R. , Bonrath W. , Gum A. 
Published: August 2005

AbstractNew insights into the energy efficiency of reactions in a microwave field and the development of a concept to transfer thermally heated reactions to microwave‐assisted reactions are reported utilizing commercial modular microwave systems. Particularly, questions on the qualification of technical microwave systems and their measurement and monitoring technology as well as on the validation of chemical reactions and processes are discussed. For that purpose, some technical microwave systems of different manufacturers were tested. The applicability for the implementation of chemical reactions and processes was determined. Conversions and yields of some reactions were compared by the dependence of irradiation modus, temperature and temperature measurement method.