bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of thyroid hormones on circulating markers of cell-mediated immune response, as studied in patients with differentiated thyroid carcinoma before and during thyroxine withdrawal
Authors: Botella-Carretero José I , Prados Aranzazu , Manzano Luis , Montero María T , Escribano Luis , Sancho José , Escobar-Morreale Héctor F
Published: August 2005

Objective: To address the influence of thyroid hormones on circulating markers of cell-mediated immune response in anin vivohuman model.

Subjects and design: Twenty-two patients with stage I differentiated thyroid carcinoma were studied on the last day of thyroxine suppressive treatment, 4–7 days after withdrawal, and the day before whole body scanning. Three patients were excluded because of residual disease. Twenty euthyroid individuals served as controls. Serum thyrotrophin and thyroid hormones were measured by an immunometric assay, circulating cytokines by enzyme-linked immuno-sorbent assay and lymphoid populations by flow cytometry.

Results: Thyroid function in patients changed from subclinical or mild hyperthyroidism at the first visit, to a situation of normal circulating levels of free thyroxine and triiodothyronine at the second, ending in a state of overt hypothyroidism. Thyroxine suppressive treatment in patients increased serum interleukin-18 concentrations (IL-18, mean±s.d., 280±122 vs 183±106 pg/ml, F = 3.192,P= 0.029), soluble interleukin-2 receptor levels (sIL-2R, 4368±1480 vs 2564±846 pg/ml, F = 21.324,P< 0.001), and the percentage of natural killer (NK) cells in peripheral blood (15.9±8.6 vs 10.5±3.6%, F = 4.977,P= 0.004) compared with controls. After thyroxine withdrawal, serum levels of IL-18, sIL-2R and the percentage of NK cells decreased progressively.

Conclusion: Our present results suggest that thyroid hormones modulate the cell-mediated immune response in humans.
Expression of renal 11β-hydroxysteroid dehydrogenase type 2 is decreased in patients with impaired renal function
Authors: Quinkler Marcus , Zehnder Daniel , Lepenies Julia , Petrelli Massimiliano D , Moore Jasbir S , Hughes Susan V , Cockwell Paul , Hewison Martin , Stewart Paul M
Published: August 2005

Objective: Renal 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) enables selective access of aldosterone to the mineralocorticoid receptor (MR). Impaired 11β-HSD2 activity has been suggested in patients with hypertension as well as in patients with renal disease, where it may contribute to sodium retention, oedema and hypertension. To date, these studies have relied upon urinary cortisol (F) metabolite levels as surrogate markers of renal 11β-HSD2 activity.

Methods: We have directly analysed renal 11β-HSD2 mRNA expression in 95 patients undergoing kidney biopsy using TaqMan real-time PCR. Serum and 24-h urine samples were used to document underlying renal function and endocrine parameters. Urinary F and cortisone (E) metabolites were analysed using gas chromatography/mass spectrometry.

Results: Expression of 11β-HSD2 did not correlate with blood pressure or urinary Na/K ratio, but a significant positive correlation with creatinine clearance was observed (r= 0.284;P< 0.01). Immunofluorescence and confocal laser microscopy confirmed decreased 11β-HSD2 expression in patients with impaired renal function. For the first time, we showed that 11β-HSD2 mRNA expression correlated negatively with the urinary free (UF) F/E (UFF/UFE) ratio (r= 0.276;P< 0.05) as well as with the urinary tetrahydrocortisol + 5α-tetrahydrocortisol/tetrahydrocortisone ((THF + αTHF)/THE) ratio (r= 0.256;P< 0.05). No difference in 11β-HSD2 mRNA expression or in the UFF/UFE ratio was found between groups with no proteinuria, microalbuminuria, moderate or severe proteinuria. In contrast, the urinary (THF + αTHF)/THE ratio increased significantly (P< 0.05) in patients with severe albuminuria, suggesting increased hepatic 11β-HSD1 in those patients.

Conclusions: These data suggest that renal 11β-HSD2 expression may be represented only marginally better, if at all, by the UFF/UFE than by the (THF + αTHF)/THE ratio. Reduced renal 11β-HSD2 expression may lead to occupancy of the MR by glucocorticoids such as cortisol and may contribute to the increased sodium retention seen in patients with impaired renal function.
Pegvisomant therapy in pituitary gigantism: successful treatment in a 12-year-old girl
Authors: Rix M , Laurberg P , Hoejberg A S , Brock-Jacobsen B
Published: August 2005

Objective: The use of a growth hormone (GH) receptor antagonist, pegvisomant has shown great promise in adults with acromegaly, but experience in paediatric patients is lacking. We aimed to describe the results of pegvisomant therapy in a 12-year-old girl with an aggressive GH-secreting pituitary tumour.

Design: To evaluate the ability of pegvisomant therapy to control the effects of peripheral GH excess in a case of pituitary gigantism.

Methods: Pegvisomant was introduced at 10 mg/day, given subcutaneously, and gradually increased to 20 mg/day until serum IGF-I was normal for age.

Results: A large pituitary adenoma with suprasellar extension was diagnosed in a 12-year-old girl with progressive tall stature (178 cm), GH hypersecretion without suppression during oral glucose loading (nadir serum GH, 90 mU/l), high serum IGF-I and serum prolactin levels. Surgical extirpation was not possible because tumour tissue was fibrous and adherent to the optical nerves. Histological examination showed a mixed GH- and prolactin-secreting adenoma with lymphocytic infiltration of B and T cells. Treatment with a dopamine agonist, cabergoline, normalized serum prolactin, but GH secretion was resistant to both somatostatin analogue, octreotide and cabergoline. Radiation followed by pegvisomant therapy titrated up in dose to 20 mg/day led to a marked reduction in GH secretion and normalization of IGF-I, and to growth arrest and improvement of well-being.

Conclusions: We suggest that treatment in pituitary gigantism with pegvisomant is safe and may normalize IGF-I levels and effectively stop growing.
Machine learning approaches for phenotype–genotype mapping: predicting heterozygous mutations in the CYP21B gene from steroid profiles
Authors: Prank Klaus , Schulze Egbert , Eckert Olaf , Nattkemper Tim W , Bettendorf Markus , Maser-Gluth Christiane , Sejnowski Terrence J , Grote Arno , Penner Erika , von zur Mühlen Alexander , Brabant Georg
Published: August 2005

Objective: Non-linear relations between multiple biochemical parameters are the basis for the diagnosis of many diseases. Traditional linear analytical methods are not reliable predictors. Novel nonlinear techniques are increasingly used to improve the diagnostic accuracy of automated data interpretation. This has been exemplified in particular for the classification and diagnostic prediction of cancers based on expression profiling data. Our objective was to predict the genotype from complex biochemical data by comparing the performance of experienced clinicians to traditional linear analysis, and to novel non-linear analytical methods.

Design and methods: As a model, we used a well-defined set of interconnected data consisting of unstimulated serum levels of steroid intermediates assessed in 54 subjects heterozygous for a mutation of the 21-hydroxylase gene (CYP21B) and in 43 healthy controls.

Results: The genetic alteration was predicted from the pattern of steroid levels with an accuracy of 39% by clinicians and of 64% by linear analysis. In contrast, non-linear analysis, such as self-organizing artificial neural networks, support vector machines, and nearest neighbour classifiers, allowed for higher accuracy up to 83%.

Conclusions: The successful application of these non-linear adaptive methods to capture specific biochemical problems may have generalized implications for biochemical testing in many areas. Nonlinear analytical techniques such as neural networks, support vector machines, and nearest neighbour classifiers may serve as an important adjunct to the decision process of a human investigator not ‘trained’ in a specific complex clinical or laboratory setting and may aid them to classify the problem more directly.
Corticotroph adenoma of the pituitary in a patient with X-linked adrenal hypoplasia congenita due to a novel mutation of the DAX-1 gene
Authors: De Menis Ernesto , Roncaroli Federico , Calvari Vladimiro , Chiarini Valerio , Pauletto Paolo , Camerino Giovanna , Cremonini Nadia
Published: August 2005

Objective: Mutations in the DAX-1 gene result in X-linked congenital adrenal hypoplasia. The classic clinical presentation is primary adrenal insufficiency in early life and hypogonadotropic hypogonadism at the time of expected puberty, but recent data have expanded the phenotypic spectrum of DAX-1 mutations. We report the occurrence of an ACTH-secreting adenoma in a patient with X-linked congenital adrenal hypoplasia.

Design and methods: Detailed clinical, radiological and pathological investigation of the pituitary adenoma. Genomic analysis of the DAX-1 gene in the patient and his mother.

Results: In this patient, primary adrenal failure had been diagnosed at 3 years of age and, despite replacement therapy, at 30 years of age progressive pigmentation developed and impairment of the visual field followed. ACTH was 24 980 pg/ml and nuclear magnetic resonance disclosed a huge pituitary adenoma. Three transsphenoidal operations and radiotherapy were necessary to remove the tumor mass and control ACTH secretion. Histologically, the adenoma was composed of chromophobic and basophilic neoplastic cells with positive immunostaining for ACTH. Moreover, a novel mutation was found both in the patient and his mother: a 4 bp insertion (AGCG) at nucleotide 259, in exon 1 resulting in a frame shift and premature termination.

Conclusions: This case suggests that in adrenal hypoplasia congenita the development of a pituitary adenoma should be considered when a sudden rise of ACTH occurs despite adequate steroid substitution.
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.
Markers of cell proliferation in a GH-producing adenoma of a patient treated with pegvisomant
Authors: Drake W M , Berney D M , Kovacs K , Monson J P
Published: August 2005

We report our findings on markers of cell proliferation (Ki-67 labelling index and topoisomerase-α expression) in a somatotroph pituitary tumour before and after exposure to pegvisomant, a GH receptor antagonist developed for the treatment of acromegaly. Specimens from two separate pituitary operations, separated by a period of 17 years that included 4 years of pegvisomant treatment, were stained for markers of cellular proliferation. Ki-67 labelling index and topoisomerase-α expression were both markedly greater (1–3% compared with 0–0.5% and 15–80% compared with 2–10% respectively) in the pegvisomant-exposed tumour compared with the earlier specimen. Clearly, caution must be exercised when interpreting findings from a single case, particularly one sufficiently refractory to conventional therapies to require treatment with pegvisomant. However, our data reinforce the requirement for careful radiological surveillance of the pituitary in the context of a drug that does not target the tumour responsible and where serum GH cannot serve as a marker of disease activity or tumour size.
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

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

Recent 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

Lysosomes 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

Self‐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

Cornelia 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

New 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.
Preparation and Reactivity of [D3d]‐Octahedrane: The Most Stable (CH)12 Hydrocarbon
Authors: de Meijere Armin , Lee Chi‐Hung , Kuznetsov Mikhail A. , Gusev Dmitriy V. , Kozhushkov Sergei I. , Fokin Andrey A. , Schreiner Peter R.
Published: August 2005

The synthesis of the (CH)12 hydrocarbon [D3d]‐octahedrane (heptacyclo[6.4.0.02,4.03,7.05,12.06,10.09,11]dodecane) 1 and its selective functionalization retaining the hydrocarbon cage is described. The B3LYP/6‐311+G* strain energy of 1 is 83.7 kcal mol−1 (4.7 kcal mol−1 per CC bond) which is significantly higher than that of the structurally related (CH)16 [D4d]‐decahedrane 2 (75.4 kcal mol−1; 3.1 kcal mol−1 per CC bond) and (CH)20 [Ih]‐dodecahedrane 3 (51.5 kcal mol−1; 1.7 kcal mol−1 per CC bond); the heats of formation for 1–3 computed according to homodesmotic equations are 52, 35, and 4 kcal mol−1. Catalytic hydrogenation of 1 leads to consecutive opening of the two cyclopropane rings to give C2‐bisseco‐octahedrane (pentacyclo[6.4.0.02,6.03,11.04,9]dodecane) 16 as the major product. Although 1 is highly strained, its carbon skeleton is kinetically quite stable: Upon heating, 1 does not decompose until above 180 °C. The B3LYP/6‐31G* barriers for the SR2 attack of the tBuO. and Br3C. radicals on a carbon atom of one of the cyclopropane fragments (Δ${G{{\,{\ne}\hfill \atop 298\hfill}}}$ = 27–28 kcal mol−1) are higher than those for hydrogen atom abstraction. The latter barriers are virtually identical for the abstraction from the C1‐H and C2‐H positions with the tBuO. radical (Δ${G{{\,{\ne}\hfill \atop 298\hfill}}}$ = 17.4 and 17.9 kcal mol−1, respectively), but significantly different for the reaction at these positions with the Br3C. radical (Δ${G{{\,{\ne}\hfill \atop 298\hfill}}}$ = 18.8 and 21.0 kcal mol−1). These computational results agree well with experiments, in which the chlorination of 1 with tert‐butyl hypochlorite gave a mixture of 1‐ and 2‐chlorooctahedranes (ratio 3:2). The bromination with carbon tetrabromide under phase‐transfer catalytic (PTC) conditions (nBu4NBr/NaOH) selectively gave 1‐bromooctahedrane in 43 % isolated yield. For comparison, the PTC bromination was also applied to 2,4‐dehydroadamantane yielding 54 % 7‐bromo‐2,4‐dehydroadamantane.
Highly Modular Synthesis of C1‐Symmetric Aminosulfoximines and Their Use as Ligands in Copper‐Catalyzed Asymmetric Mukaiyama‐Aldol Reactions
Authors: Langner Martin , Rémy Pauline , Bolm Carsten
Published: August 2005

The development of C1‐symmetric aminosulfoximines, their highly modular synthesis, and their application in enantioselective copper‐catalyzed Mukaiyama‐type aldol reactions between pyruvates and enolsilanes is described. In this context, the influence of the ligand architecture as well as the optimization of the reaction conditions are discussed. In detail, the dependence of the catalyst efficiency on the solvent, the metal source and the temperature are reported, and an interesting additive effect is highlighted. Furthermore, the substrate scope will be presented. With the optimized catalyst system, a number of aldol products with quaternary stereogenic centers have been obtained in high yields and with enantiomeric excesses up to 99 %.
Mild and Solvent‐Free Alkynylation of Ketones on the KF/Alumina.
Authors: Sharifi Ali , Mirzaei Mojtaba , Naimi‐Jamal M. Reza
Published: August 2005

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An Economical, Highly Efficient and Recyclable Catalyst System for Asymmetric Dihydroxylation of Olefins.
Authors: Jin Ying , Sun Xiao‐Li , Jiang Ru , Zhang Sheng‐Yong
Published: August 2005

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Long Chain Phenols. Part 40. The Synthesis of Thiobisphenols from 3‐Alkylphenols Derived from Natural Phenolic Lipids.
Authors: Tyman John H. P. , Johnson Robert A.
Published: August 2005

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Carbonic Anhydrase Inhibitors: Synthesis and Inhibition of Cytosolic/Tumor‐Associated Carbonic Anhydrase Isozymes I, II, and IX with Sulfonamides Incorporating Thioureido‐Sulfanilyl Scaffolds.
Authors: Puccetti Luca , Fasolis Giuseppe , Cecchi Alessendro , Winum Jean‐Yves , Gamberi Alessandro , Montero Jean‐Louis , Scozzafava Andrea , Supuran Claudiu T.
Published: August 2005

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Synthesis of the New 5‐(Fluorobenzenethiolated)‐2‐furfuraldehyde Thiosemicarbazones
Authors: Bautista Juan L. , Tiburcio Jorge , Torrens Hugo
Published: August 2005

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Electrochemical Fluorination of Several Esters Derived from Oxolane‐2‐yl‐carboxylic Acid, Oxolane‐2‐yl‐methanol and Oxane‐2‐yl‐methanol.
Authors: Abe Takashi , Tamura Masanori , Sekiya Akira
Published: August 2005

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An Efficient Synthesis of Bis(indolyl)methanes Catalyzed by Recycled Acidic Ionic Liquid.
Authors: Gu Da‐Gong , Ji Shun‐Jun , Jiang Zhao‐Qin , Zhou Min‐Feng , Loh Teck‐Peng
Published: August 2005

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Synthesis and Reductive Reactions of 2,3‐Dioxo‐2,3‐dihydrobenzo[b]furo[2,3‐f]‐, ‐[2,3‐g]‐, and ‐[3,2‐e]indoles.
Authors: Khoshtariya T. E. , Matnadze M. M. , Mirziashvili N. T. , Kurkovskaya L. N. , Sikharulidze M. I. , Dzhashi T. O.
Published: August 2005

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I2‐Mediated Photochemical Preparation of 2‐Substituted 1,3‐Dioxolanes and Tetrahydrofurans from Alcohols with Polymer‐Supported Hypervalent Iodine Reagent, PSDIB.
Authors: Teduka Tomomasa , Togo Hideo
Published: August 2005

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Microwave‐Assisted from Synthesis of 2‐Arylamino‐2‐imidazolines on a Solid Support.
Authors: Genc Murat , Servi Sueleyman
Published: August 2005

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Synthesis, Analgesic and Antiinflammatory Properties of Certain 5‐/6‐Acyl‐3‐(4‐substituted‐1‐piperazinylmethyl)‐2‐benzoxazolinones Derivatives.
Authors: Koeksal Meric , Goekhan Nesrin , Kuepeli Esra , Yesilada Erdem , Erdogan Hakki
Published: August 2005

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Efficient One‐Pot Synthesis of 1,2,3‐Triazoles from Benzyl and Alkyl Halides.
Authors: Kacprzak Karol
Published: August 2005

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A Novel and Simple Synthesis of 2‐(Trifluoromethyl)‐4H‐thiochromen‐4‐ones
Authors: Usachev Boris I. , Sosnovskikh Vyacheslav Ya. , Shafeev Mikhail A. , Roeschenthaler Gerd‐Volker
Published: August 2005

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Preparation of Cyanopyridines by Direct Cyanation.
Authors: Katritzky Alan R. , Scriven Eric F. V. , Majumder Suman , Tu Hongbin , Vakulenko Anatoliy V. , Akhmedov Novruz G. , Murugan Ramiah
Published: August 2005

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A Mild and Efficient Synthesis of 2,5‐Disubstituted 2,3‐Dihydro‐4‐pyridones Catalyzed by Yb(OTf)3.
Authors: Cheng Ke , Zeng Baiqing , Yu Zhipeng , Gao Bo , Feng Xiaoming
Published: August 2005

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Synthesis of 6‐Aryl‐1,6‐dihydrodipyrazolo[3,4‐b:4,3‐c]pyridines
Authors: Vovk M. V. , Mel'nichenko N. V. , Sukach V. A. , Chubaruk N. G.
Published: August 2005

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Studies in Thio‐Claisen Rearrangement. Synthesis of Thieno‐[3,2‐c]‐quinolone Derivatives from 4‐Allylthioquinolin‐2‐(1H)‐ones.
Authors: Majumdar K. C. , Saha D. , Ghosh M.
Published: August 2005

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Green Chemical Multi‐Component One‐Pot Synthesis of Fluorinated 2,3‐Disubstituted Quinazolin‐4(3H)‐ones under Solvent‐Free Conditions and Their anti‐Fungal Activity.
Authors: Dandia Anshu , Singh Ruby , Sarawgi Pritima
Published: August 2005

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Synthesis of Medium‐ and Large‐Sized Lactones in an Aqueous—Organic Biphasic System.
Authors: Kinoshita Hidenori , Shinokubo Hiroshi , Oshima Koichiro
Published: August 2005

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Palladium‐Catalyzed Addition of Cyanoboranes to Alkynes: Regio‐ and Stereoselective Synthesis of α,β‐Unsaturated β‐Boryl Nitriles.
Authors: Suginome Michinori , Yamamoto Akihiko , Murakami Masahiro
Published: August 2005

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Molecular Design of Sweet Tasting Compounds Based on 3β‐Amino‐3β‐deoxy‐18β‐glycyrrhetinic Acid: Amido Functionality Eliciting Tremendous Sweetness.
Authors: Ijichi So , Tamagaki Seizo
Published: August 2005

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Succinct Synthesis of β‐Amino Acids via Chiral Isoxazolines.
Authors: Fuller Amelia A. , Chen Bin , Minter Aaron R. , Mapp Anna K.
Published: August 2005

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[3 + 3] Cycloadditons and Related Strategies in Alkaloid Natural Product Synthesis
Authors: Harrity Joseph P. A. , Provoost Olivier
Published: August 2005

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New Carbon‐Rich Materials for Electronics, Lithium Battery, and Hydrogen Storage Applications
Authors: Grimsdale Andrew C. , Wu Jishan , Muellen Klaus
Published: August 2005

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Recent Results in Chemistry and Biology of Nitroxides
Authors: Hideg Kalman , Kalai Tamas , Sar Cecilia P.
Published: August 2005

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“ESHC (Sopron) Plenary Lecture” Exciting Fields in P‐Heterocyclic Chemistry
Authors: Keglevich Gyoergy
Published: August 2005

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Green Chemistry — Suzuki Cross Coupling in Aqueous Media
Authors: Franzen Robert , Xu Youjun
Published: August 2005

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Creating Chemical Diversity Space by Scaffold Decoration of Dihydropyrimidines
Authors: Dallinger Doris , Kappe C. Oliver
Published: August 2005

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Toward the Library Generation of Natural Product Like Polycyclic Derivatives by Stereocontrolled Diversity‐Oriented Synthesis
Authors: Arya P. , Quevillon S. , Joseph R. , Wei C.‐Q. , Gan Z. , Parisien M. , Sesmilo E. , Reddy P. T. , Chen Z.‐X. , Durieux P. , et al. et al.
Published: August 2005

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Use of Furans in the Synthesis of Bioactive Compounds
Authors: Lee Hing‐Ken , Chan Kin‐Fai , Hui Chi‐Wai , Yim Ho‐Kee , Wu Xun‐Wei , Wong Henry N. C.
Published: August 2005

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Carbanions and Electrophilic Aliphatic Substitution
Authors: Knipe A. C.
Published: August 2005

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Novel Biocatalyst Technology for the Preparation of Chiral Amines
Authors: Turner Nicholas , Fotheringham Ian , Speight Robert
Published: August 2005

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Boron
Authors: Weller A. S.
Published: August 2005

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Microwave‐Assisted Organic Syntheses: Applications. Part 29. Rearrangements
Authors: Keller Walter E.
Published: August 2005

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Preparation of New Nitrogen‐Bridged Heterocycles Using Pyridinium N‐Ylides and Pyridinium Salts
Authors: Kakehi Akikazu
Published: August 2005

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Preparation of Poly(diazo) Compounds as Precursors of Organo‐Magnetic Materials by Utilizing Diazo Compound as Building Blocks
Authors: Itoh Tetsuji , Hirai Katsuyuki , Tomioka Hideo
Published: August 2005

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Solvatochromic Probes in Supercritical Fluids
Authors: Marcus Yizhak
Published: August 2005

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Molecular Taxonomy and Epidemiology of Cystic Echinococcosis
Authors: McManus D. P.
Published: August 2005

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Sodium and Sulfur Process Chemistry in Black Liquor Gasification and Combustion: Review and Reevaluation of Basic Thermochemical Data
Authors: Larsson Anders , Lindberg Gustav , Raberg Mathias , Nordin Anders , Bostroem Dan , Rosen Erik , Warnqvist Bjoern , Backman Rainer
Published: August 2005

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EPR Spectrometers at Frequencies Below X‐Band
Authors: Eaton Gareth R. , Eaton Sandra S.
Published: August 2005

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Light‐Driven Unidirectional Rotation in a Molecule: ROKS Simulation
Authors: Grimm Stephan , Bräuchle Christoph , Frank Irmgard
Published: August 2005

We present a first‐principles molecular dynamics study of the excited‐state motion in a molecule that has recently been proven to exhibit light‐driven unidirectional rotation. The simulations show that the directed motion is due to the complex excited‐state dynamics on ultrashort timescales in the chiral system.
Unusual Temperature Effects in Propene Polymerization Using Stereorigid Zirconocene Catalysts
Authors: Jensen Vidar R. , Graf Martin , Thiel Walter
Published: August 2005

Free Car–Parrinello molecular dynamics (CPMD) simulations of four diastereomers of the zirconium–propene complexes [{iPr(3‐iPr‐CpFlu)}ZriBu(C3H6)]+ (Cp=cyclopentadienyl; Flu=fluorenyl) provide valuable insight into the mechanism and stereocontrol of propene polymerization with stereorigid metallocenes. Spontaneous insertion of propene into the zirconium–isobutyl bond is not observed, and propene is found to be weakly bound and to rotate relatively freely around the CC bond to be formed. Large‐amplitude rotation of the isopropyl substituent around the CpiPr bond may play a role in triggering dissociation of propene. Three of the four diastereomers eliminate propene during the course of the simulations, which makes dissociation the dominating event on a 20‐ps timescale. The CPMD simulations thus support the validity of the assumption, fundamental to statistical propagation models, that each insertion is independent of the preceding insertions. Using insertion barriers from static density functional calculations, the statistical model predicts the polypropene microstructure in good agreement with experiment at low polymerization temperatures for the catalysts {iPr(3‐R‐CpFlu)}ZrCl2 (R=H, iPr, tBu). The predictions become less accurate at higher temperatures, probably due to the onset of the competing back‐skip reaction, which is not included in the model.