bluuebunny/crossref_metadata_2025 huggingface dataset:
Cooperation and Competition in Intergenerational Experiments in the Field and the Laboratory
Authors: Charness Gary , Villeval Marie-Claire
Published: June 2009

There is economic pressure to postpone the retirement age, but employers are still reluctant to employ older workers. We investigate the comparative behavior of juniors and seniors in experiments conducted both onsite with the employees of two large firms and in a conventional laboratory environment with students and retirees. We show that seniors are no more risk averse than juniors and are typically more cooperative; both juniors and working seniors respond strongly to competition. The implication is that it may be beneficial to define additional incentives near the end of the career to motivate and retain older workers. (JEL C90, J14, J26, M12, M51)
Transfreight Reduces Costs and Balances Workload at Georgetown Crossdock
Authors: Rosales Claudia R. , Fry Michael J. , Radhakrishnan Rajesh
Published: June 2009

Transfreight, LLC, is a third-party logistics provider that supports Toyota Motor Manufacturing's operations in North America. As part of its logistical support, the company operates several crossdocks that facilitate Toyota's focus on lean manufacturing principles. In this paper, we describe our development of a mixed-integer linear program that provides optimal allocation of inbound trailers to docks at a crossdock facility. We focus on improving its operational efficiency and balancing the workload of the crossdock workers. We discuss Transfreight's successful implementation of our model for its inbound trailer assignments at its largest crossdock in Georgetown, Kentucky. Our work has provided Transfreight with significant cost savings and growth opportunities.
An Integrated Outbound Logistics Model for Frito-Lay: Coordinating Aggregate-Level Production and Distribution Decisions
Authors: Çetinkaya Sıla , Üster Halit , Easwaran Gopalakrishnan , Keskin Burcu Baris
Published: June 2009

In this paper, we describe research to improve Frito-Lay's outbound supply chain activities by simultaneously optimizing its inventory and transportation decisions. Motivated by Frito-Lay's practice, we first develop a mixed-integer programming formulation from which we develop a large-scale, integrated multiproduct inventory lot-sizing and vehicle-routing model with explicit (1) inventory holding costs, truck loading and dispatch costs, and mileage costs; (2) production, storage, and truck capacity limitations; and (3) direct (plant-to-store) and interplant (plant-to-plant) delivery considerations. Second, we present an iterative solution approach in which we decompose the problem into inventory and routing components. The results demonstrate the impact of direct deliveries on distribution costs and show that direct deliveries and efficient inventory and routing decisions can provide significant savings opportunities over two benchmark models, one of which represents the existing Frito-Lay system. We implemented our models using an application that allows strategy evaluation, analysis of output files, and technology transfer. This application was particularly useful in evaluating potential direct-delivery locations and inventory reductions throughout the supply chain.
Organizational Ambidexterity: Balancing Exploitation and Exploration for Sustained Performance
Authors: Raisch Sebastian , Birkinshaw Julian , Probst Gilbert , Tushman Michael L.
Published: June 2009

Organizational ambidexterity has emerged as a new research paradigm in organization theory, yet several issues fundamental to this debate remain controversial. We explore four central tensions here: Should organizations achieve ambidexterity through differentiation or through integration? Does ambidexterity occur at the individual or organizational level? Must organizations take a static or dynamic perspective on ambidexterity? Finally, can ambidexterity arise internally, or do firms have to externalize some processes? We provide an overview of the seven articles included in this special issue and suggest several avenues for future research.
Hiring Stars and Their Colleagues: Exploration and Exploitation in Professional Service Firms
Authors: Groysberg Boris , Lee Linda-Eling
Published: June 2009

This paper examines exploration and exploitation in professional service firms by focusing on the individuals who carry out the exploration and exploitation activities. Specifically, we examine the performance of star security analysts who join new firms in exploration versus exploitation roles. We find that stars hired to explore (initiate new activities) experience a short- and long-term performance decline; by contrast, stars who join new firms to exploit (reinforce existing activities) suffer only a short-term drop in performance. Stars hired in exploration roles can preserve some of their performance by moving with a group of colleagues from the originating firm. Investors view the hiring of a star analyst as value-destroying for the hiring firm regardless of whether the firm is hiring to exploit or explore, but the negative reactions are economically more extreme for exploration hires. These findings indicate that, even at the individual level, probabilities of success in exploration activities are lower than in exploitation activities, thereby reinforcing the tendency toward exploitation.
The process of recovery from bipolar I disorder: A qualitative analysis of personal accounts in relation to an integrative cognitive model
Authors: Mansell Warren , Powell Seth , Pedley Rebecca , Thomas Nia , Jones Sarah Amelia
Published: June 2009

Objectives. This study explored the process of recovery from bipolar I disorder from a phenomenological and cognitive perspective.

Design. A semi‐structured interview was coded and analysed using interpretative phenomenological analysis.

Methods. Eleven individuals over the age of 30 with a history of bipolar disorder were selected on the basis of having remained free from relapse, and without hospitalization for at least 2 years, as confirmed by a diagnostic interview (Standardised Interview for DSM‐IV; SCID‐I). This arbitrary and equivocal criterion for ‘recovery’ provided an objective method of defining the sample for the study.

Results. The analysis revealed two overarching themes formed from four themes each. Ambivalent approaches referred to approaches that participants felt had both positive and negative consequences: avoidance of mania, taking medication, prior illness versus current wellness, and sense of identity following diagnosis. Helpful approaches referred to approaches that were seen as universally helpful: understanding, life‐style fundamentals, social support and companionship, and social change.

Conclusions. These themes were then interpreted in the light of the existing literature and an integrative cognitive model of bipolar disorder. Limitations and future research directions are discussed.
Come together: Two studies concerning the impact of group relations on personal space
Authors: Novelli David , Drury John , Reicher Steve
Published: June 2009

This paper describes two experiments investigating the impact of group relations on personal space. In Study 1, participants (N =39) in minimal groups were told that they would be interacting with another person. In line with expectations, personal space (as measured by the distance between chairs) was significantly less in the intragroup context than in the intergroup and interpersonal contexts. This finding was replicated in Study 2 (N =80) using an improved experimental design. These results are discussed in terms of developing a self‐categorization account of personal space and crowding.
Relationship between coping with negative life‐events and psychopathology: Major depression and borderline personality disorder
Authors: Wingenfeld Katja , Mensebach Christoph , Rullkoetter Nina , Schlosser Nicole , Schaffrath Camille , Beblo Thomas , Driessen Martin
Published: June 2009

Ninety psychiatric in‐patients and 73 controls have been asked about their coping styles to negative life‐events. Patients reported more emotion‐oriented coping than controls. Emotion‐oriented coping style was positively correlated with psychopathology, while task‐oriented coping was negatively correlated with psychopathology in events which the participants had difficulties dealing with.
Serum Free Light Chain Ratio, Total κ/λ Ratio, and Immunofixation Results Are Not Prognostic Factors after Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma
Authors: Giarin Manuela M , Giaccone Luisa , Sorasio Roberto , Sfiligoi Christian , Amoroso Barbara , Cavallo Federica , Cipriani Alessia , Palumbo Antonio , Boccadoro Mario
Published: June 2009

Background: The prognostic value of changes in paraprotein markers after stem cell transplantation is unknown. We evaluated disease response using serum immunofixation (s-IFIX), total κ and λ ratio (KLR), and free light chain (FLC) ratio in myeloma patients who underwent autologous or autologous plus allogeneic stem cell transplantation.

Methods: We studied s-IFIX, KLR, and FLC ratio in sera from 203 patients, 3 months after transplantation. We evaluated overall and event-free survival (OS and EFS, interval between date of study enrollment and date of death from any cause or date of progression, relapse, or death from any cause, respectively) by the Kaplan–Meier method.

Results: Of the 203 patients, 51 were negative by s-IFIX, 99 reached a normal KLR, and 92 had a normal FLC ratio. Of the 51 patients with negative s-IFIX, 40 (78%) also had a normal FLC ratio. The median duration of OS was 54.3 months, and the median EFS was 19.5 months. None of the measured paraprotein parameters showed an association with OS. Only a normal KLR was associated with prolonged EFS (P = 0.016). Even a negative s-IFIX associated with a normal FLC ratio did not show a significant difference in terms of EFS and OS.

Conclusions: Our analysis with a small cohort of patients did not show a significant impact of achieving complete response (CR) or stringent CR on patient survival.
Quantitation of Serum Monoclonal Proteins: Relationship between Agarose Gel Electrophoresis and Immunonephelometry
Authors: Murray David L , Ryu Euijung , Snyder Melissa R , Katzmann Jerry A
Published: June 2009

Background: Previous comparisons of monoclonal protein quantification identified a bias between serum protein electrophoresis (SPEP) and immunonephelometry (NEPH).

Methods: We reviewed data from 2845 patients in whom a single sample provided a γ fraction M-spike by SPEP, a heavy chain isotype by immunofixation electrophoresis (IFE), and an Ig quantification by NEPH. We examined the relationship between SPEP and NEPH. Selected sera with high monoclonal protein concentrations were diluted and reassessed.

Results: For all isotypes, the relationship between SPEP and NEPH was best fitted with cubic curves. We determined the concentrations of each isotype that fitted a linear relationship. IgA had the best correspondence (slope 0.92, 95% CI 0.87–1.02), whereas IgM demonstrated a systematic bias of higher values by NEPH (slope 1.80, 95% CI 1.68–1.92). IgG demonstrated a nonlinear relationship between SPEP and NEPH, with a linear region <19.2 g/L having a slope of 0.83 (95% CI 0.79–0.89) and a second linear region having a slope of 1.47 (95% CI 1.39–1.53) at higher concentrations. Dilutions of high-concentration IgG monoclonal proteins were linear by NEPH and nonlinear by SPEP.

Conclusions: There are systematic differences in the quantification of monoclonal IgM and IgG by SPEP and NEPH. The bias in IgM is from NEPH overestimation. The nonlinearity of SPEP at high monoclonal IgG concentrations may obscure changes in plasma cell populations. Clinicians should be made aware of the biases and nonlinearity in these tests to make proper conclusions regarding treatment response.
Self-Benefit versus Other-Benefit Marketing Appeals: Their Effectiveness in Generating Charitable Support
Authors: White Katherine , Peloza John
Published: June 2009

Despite the growing need, nonprofit organization marketers have not yet fully delineated the most effective ways to position charitable appeals. Across five experiments, the authors test the prediction that other-benefit (self-benefit) appeals generate more favorable donation support than self-benefit (other-benefit) appeals in situations that heighten (versus minimize) public self-image concerns. Public accountability, a manipulation of public self-awareness, and individual differences in public self-consciousness all moderate the effect of appeal type on donor support. In particular, self-benefit appeals are more effective when consumers’ responses are private in nature; in contrast, other-benefit appeals are more effective when consumers are publicly accountable for their responses. This effect is moderated by norm salience and is related to a desire to manage impressions by behaving in a manner consistent with normative expectations. The results have important managerial implications, suggesting that rather than simply relying on one type of marketing appeal across situations, marketers should tailor their marketing message to the situation or differentially activate public self-image concerns to match the appeal type.
Auctioning Keywords in Online Search
Authors: Chen Jianqing , Liu De , Whinston Andrew B.
Published: June 2009

Keyword advertising, or “sponsored links” that appear alongside online search results or other online content, has grown into a multibillion-dollar market. Providers of keyword advertising, such as Google and Yahoo, profit by auctioning keywords to advertisers. An issue of increasing importance for advertising providers is the “share structure” problem—that is, of the total available resources for each keyword (in terms of exposure), how large a share should be set aside for the highest bidder, for the second-highest bidder, and so on. The authors study this problem under a general specification and characterize the optimal share structures that maximize advertising providers’ revenues. They also derive results on how the optimal share structure should change with advertisers’ price elasticity of demand for exposure, their valuation distribution, total resources, and minimum bids. The authors draw implications for keyword auctions and other applications.
Evidence of changes in the immunophenotype and metabolic characteristics (intracellular reactive oxygen radicals) of fetal, but not maternal, monocytes and granulocytes in the fetal inflammatory response syndrome
Authors: Kim Sun Kwon , Romero Roberto , Chaiworapongsa Tinnakorn , Kusanovic Juan Pedro , Mazaki-Tovi Shali , Mittal Pooja , Erez Offer , Vaisbuch Edi , Gotsch Francesca , Pacora Percy , Yeo Lami , Gervasi Maria Teresa , Lamont Ronald F. , Yoon Bo Hyun , Hassan Sonia S.
Published: June 2009

Objective: The fetal inflammatory response syndrome (FIRS) is present in a fraction of fetuses exposed to intra-amniotic infection and is associated with the impending onset of labor and multisystem organ involvement. Neonates born with funisitis, the histologic counterpart of fetal systemic inflammation, are at increased risk for cerebral palsy and bronchopulmonary dysplasia. The aim of this study was to determine whether fetal and maternal granulocytes and monocytes have the phenotypic and metabolic characteristics of activation in cases with FIRS.

Study design: A case-control study was conducted with umbilical cord and maternal blood samples obtained from patients who delivered preterm with (n=30) and without funisitis (n=15). The phenotypic characteristics of granulocytes and monocytes were examined using flow cytometry and monoclonal antibodies including CD11b, CD14, CD15, CD16, CD18, CD49d, CD62L, CD64, CD66b, and HLA-DR. Intracellular reactive oxygen species (iROS) were measured at the basal state and after stimulation (oxidative burst). A P<0.01 was considered statistically significant.

Results: (1) Funisitis was associated with a significant increase in the median mean channel brightness (MCB) of CD14, CD64, and CD66b on granulocytes and the MCB of CD64 on monocytes collected from umbilical cord blood. (2) The basal iROS production and oxidative burst were higher in the umbilical cord monocytes of neonates with funisitis than in those without funisitis. (3) There were no differences in the immunophenotype, basal iROS production, and oxidative burst in maternal granulocytes or monocytes between the study groups.

Conclusion: Fetal systemic inflammation is associated with phenotypic and metabolic changes consistent with activation in fetal immune cells but not in maternal blood.
Research on Relationship between Aging State and Low-Temperature Performance of Asphalt Mixture
Authors: Lin Qi , Zheng-qi Zhang , Ai-min Sha , Hui-jun Yang
Published: June 2009

Aging phenomenon of asphalt material exists in the course of mixing, spreading, and rolling of asphalt mixture, as well as the use in the asphalt pavement. The indirect tensile strength test was used to evaluate the performance of asphalt mixtures at low-temperature under different aging conditions. As compared with the results from the original short-term aging and the long-term aging asphalt mixtures, the results show that the original asphalt mixture cannot reflect the real performance of the asphalt mixture in the field. The short-term aging specimens are more sensitive than long-term aging specimens in evaluating the performance of the asphalt mixture at low temperature. Tests results also indicate that the consideration of aging during the evaluation of asphalt pavement performance is necessary.
Factors Influencing the Leaching of Asphalt Components
Authors: Hongmei Cai , Xiaosheng Huang , Peng Wang , Yuzhen Zhang
Published: June 2009

The main applications of asphalt involve the coating of surfaces, e.g., in roads, roofs, pipes, and linings of water basins. In all of these applications, asphalt has the possibility of coming in contact with water. Such contact can lead to the leaching of components from the asphalt into the environment. Chemical oxygen demand (COD) is a method useful in evaluating the leachability of asphalt components. The leaching conditions (leaching time and temperature) and leaching medium (content of chloride and pH value) influence the COD of leachate. These were studied using the COD leaching test. For the five asphalt binders, the COD of the leachate increased with an increase in leaching time. The COD data also showed that the concentrations of components leached from styrene-butadiene-styrene (SBS) modified asphalt and oxidized asphalt were more than from neat asphalt binders. The influencing data showed that the COD of leachate increased with the increasing of temperature, but the temperature had less influence on the leachability of lower penetration grade asphalt than higher penetration grade asphalt. The leaching of asphalt binders coming from different oil sources was influenced differently by chloride. The amounts of components leached from SBS modified asphalt and oxidized asphalt were less than from neat asphalt. The influence of chloride is attributed to the salting out effect. By investigating the influence of the leachate pH on COD, it was proven that acidic conditions had the most influence on asphalt leachability, and the COD of leachate from oxidized asphalt decreased comparing to the neat asphalt. SBS modified asphalt, was best for resisting leachability by strong acid compared with neat asphalt neat asphalt.
Insulin-like growth factors and their binding proteins
Authors: Rutanen Eeva-Marja , Pekonen Fredrika
Published: June 2009

Insulin-like growth factors are important multifunctional polypeptides interacting with cell membrane receptors and soluble binding proteins. With expanding knowledge on IGF binding proteins, it is becoming evident that the IGF actions are diverse, and depend on the context set by local binding proteins. In this minireview we attempt to provide a brief summary of the recent development in this field.
Effects of one-year hormone replacement therapy on peripheral bone mineral content in patients with osteoporotic spine fractures
Authors: Resch H. , Pietschmann P. , Krexner E. , Woloszczuk W. , Willvonseder R.
Published: June 2009

A double-blind, placebo-controlled study on 31 patients with osteoporotic spine fractures was performed in order to assess the effects of one-year cyclical estrogen/gestagen replacement therapy (Trisequens, Novo) on peripheral bone mineral content and bone turnover. Bone mineral content was measured by single-photon absorptiometry with 125I before, and 6 and 12 months after start of therapy. Calcium, phosphate, alkaline phosphatase, parathyroid hormone, calcidiol, calcitonin and 2-hour urinary hydroxyproline excretion were measured to evaluate bone turnover. After 12 months, forearm bone mineral content showed a significant increase (p<0.02) in the treatment group, whereas in the control group no statistically significant change in peripheral bone mass was observed. Parameters of bone metabolism showed a decrease in hydroxyproline excretion (p<0.02) as well as alkaline phosphatase (p<0.01) and no changes in parathyroid hormone, calcidiol, and calcitonin. These results demonstrate that one-year cyclical estrogen/gestagen replacement therapy improves peripheral bone mineral content measured by single-photon absorptiometry. This effect appears to be induced by an inhibition of bone resorption.
Circadian pattern of circulating plasma ACTH, cortisol, and aldosterone in patients with β-thalassemia
Authors: Pasqualetti Paolo , Colantonio Domenico , Collacciani Antonio , Casale Raffaele , Natali Gianfranco
Published: June 2009

Plasma levels of ACTH, cortisol, and aldosterone were measured for an entire day every 2 h, starting from midnight, in 4 healthy subjects, and in 4 patients with β-thalassemia, without evidence for any endocrine disease. The subjects, after synchronized standard life conditions for 10 days, were held in constant supine position during the study. The data were analysed by the "cosinor" method. The results show significant circadian rhythms for the three biological variables in healthy subjects. In the thalassemic patients a significant circadian rhythm was detected only for cortisol and aldosterone. No rhythm was demonstrated for ACTH in the patient group. While no differences were found in mesors and acrophases for the three hormones between the two groups, a significant difference was observed regarding amplitudes. These data suggest that in β-thalassemia, the secretion rhythmicity of ACTH is modified, whereas the adrenal cortex maintains its own physiologic rhythmicity in hormone secretion.
Turnover of thyrotropin-releasing hormone in patients with chronic renal failure and chronic alcoholic liver disease
Authors: Iversen Eigil , Schmitz Ole , Laurberg Peter
Published: June 2009

Homogenates of liver and kidney tissues are efficient in degrading TRH, but the liver contains only membrane-bound pyroglutamyl aminopeptidase, active in degrading TRH at the extracellular side of cell membranes. In the present study the effect of liver and kidney failure on the degradation of infused TRH was investigated in man. In 7 uremic patients (group I) and 7 patients with chronic alcoholic liver disease (group II) plasma clearance rate, half-time of disappearance (t½) and half time of disappearance of TRH in serum in vitro (t ½p) was determined. The plasma clearance rate, t½ and t½p were, respectively, 19.8±6.2 ml · kg−1 · min−1, 6.6±1.5 min and 16.4±6.2 min in group I versus 28.2±4.8 ml · kg−1 · min−1, 9.3±2.6 min and 25.3±15 min (mean ± sd) in group II. The volume of distribution of TRH was 19.3% of the body weight in group I and 36.5% in group II. The calculated half-time in the extravascular tissue compartment (t½t) was 5.4±1.4 min in group I and 9.2±2.7 min in group II patients (mean ± sd). TRH metabolism in the uremic patients was almost identical to that previously reported in normal subjects. In the patients with chronic liver disease plasma clearance rate was significantly greater than in normal subjects, indicating an increased TRH-degrading enzyme activity in the tissue compartment. However, owing to the very large expansion of this compartment, the t½ and t½t were significantly prolonged. Hence, half-time determination of TRH is no reliable indicator of overall TRH degradation in patients with liver disease.
Renal tubular reabsorption of calcium and sodium in primary hyperparathyroidism
Authors: Kristiansen Jan H. , Brøchner-Mortensen Jens , Pedersen Kaj O. , Jensen Søren , Glud Torben
Published: June 2009

Nine patients with primary hyperparathyroidism were studied to investigate the renal tubular reabsorption of calcium and sodium. Fasting serum and urine samples were analysed, and the glomerular filtration rate and the renal plasma clearance of lithium were determined simultaneously. Comparison was made with 9 ageand sex-matched normocalcemic controls. In the proximal tubule, there was a significantly higher absolute reabsorption of calcium in patients than in controls, whereas the fractional reabsorption rate of calcium did not differ between the two groups. In the distal tubule, the absolute calcium reabsorption rate was significantly higher in the patients, whereas the fractional reabsorption rate of calcium was significantly lower than in controls. In the patient group there was a significantly positive linear correlation between the increased tubular capacity for calsium reabsorption and the absolute proximal calcium reabsorption rate, but not between the increased capacity and the absolute distal calcium reabsorption rate. No significant differences were found in the renal tubular handling of sodium between patients and controls. Our results suggest that the increased capacity for tubular calcium reabsorption in primary hyperparathyroidism mainly is localized in the proximal tubule, and that the renal tubular handling of calcium and sodium in this disease differs from that in familial hypocalciuric hypercalcemia.
Role of extracellular calcium and calmodulin in prolactin secretion induced by hyposmolarity, thyrotropin-releasing hormone, and high K+ in GH4C1 cells
Authors: Wang Xiangbing , Sato Noriyuki , Greer Monte A. , Greer Susan E. , McAdams Staci
Published: June 2009

The mechanism by which 30% medium hyposmolarity induces PRL secretion by GH4C1 cells was compared with that induced by 100 nmol/l TRH or 30 mmol/l K+. Removing medium Ca2+, blocking Ca2+ channels with 50 μmol/l verapamil, or inhibiting calmodulin activation with 20 μmol/l trifluoperazine, 10 μmol/l chlorpromazine or 10 μmol/l pimozide almost completely blocked hyposmolarity-induced secretion. The smooth muscle relaxant, W-7, which is believed relatively specific in inhibiting the Ca2+-calmodulin interaction, depressed hyposmolarity-induced PRL secretion in a dose-dependent manner (r = −0.991, p<0.01 ). The above drugs also blocked or decreased high K+-induced secretion, but had much less effect on TRH-induced secretion. Secretion induced by TRH, hyposmolarity, or high K+ was optimal at pH 7.3-7.65 and was significantly depressed at pH 6.0 or 8.0, indicating that release of hormone induced by all 3 stimuli is due to an active cell process requiring a physiologic extracellular pH and is not produced by nonspecific cell toxicity. The data suggest hyposmolarity and high K+ may share some similarities in their mechanism of stimulating secretion, which is different from that of TRH.
Production of 21-deoxyaldosterone by rat adrenal tissue in vitro; evidence for an alternative biosynthetic pathway of aldosterone
Authors: Lewicka Sabina , Bige Katharina , Weindel Kurt , Winter Jeanette , Pies Wolfgang , Vecsei Paul
Published: June 2009

Quartered rat adrenal glands transformed labelled 21-deoxyaldosterone into aldosterone in vitro. 21-deoxyaldosterone was released from the quartered rat adrenals in vitro in amounts 10 times lower than those of aldosterone and 18-hydroxycorticosterone. The production of all three steroids was qualitatively dependent on the same regulatory elements (electrolytes, ACTH, exogenous precursors, zonal specificity). However, quantitative differences could be observed. The results support a role for 21-deoxyaldosterone as a facultative precursor of aldosterone and indicate that the regulation of its production shows similarities to that of aldosterone.
Growth hormone secretion patterns in relation to LH and testosterone secretion throughout normal male puberty
Authors: Wennink Johanna M. B. , de Waal Henriette A. Delemarre-van , Schoemaker Rik , Blaauw Gert , van den Braken Caro , Schoemaker Joop
Published: June 2009

Pulsatile growth hormone secretion patterns were studied in relation to LH and testosterone release in 30 healthy prepubertal boys and 2 adult men. Plasma GH was measured every 10 min, plasma LH and testosterone every hour. Night-time GH secretion parameters were 2-3 times higher than daytime values. During daytime, mean GH level and the fraction of GH in pulses increased from Tanner stage G2 to G4 (p=0.01); during night-time these parameters increased as well (p≤0. 1) and decreased from stage G5 to adulthood (p=0.05). GH pulse number did not increase; the number of high-amplitude (>8 μg/l pulses, however, increased from stage G2 to G4 (p=0.05) during the day. Height velocity correlated with the number of high pulses during day and night (τ=0.39, p<0.003). From stage G2 to G4 significant correlations were observed between nocturnal testosterone levels and GH secretion parameters (τ=0.53-0.57), in contrast to nocturnal LH levels. It is concluded that during puberty 1. GH secretion increases as a result of an increased pulse amplitude; 2. there is no consistent correlation between GH and LH levels; 3. increasing nocturnal testosterone levels are correlated with the increasing GH secretion; therefore GnRH does not seem to influence GH secretion directly, but an indirect effect via testosterone is more conceivable, and 4. height velocity is correlated with the number of high GH pulses.
Simultaneous measurement of TSH-binding inhibitor immunoglobulin and thyroid stimulating autoantibody activities using cultured FRTL-5 cells in patients with untreated Graves' disease
Authors: Lu Chao , Kasagi Kanji , Hidaka Akinari , Hatabu Hiroto , Iida Yasuhiro , Konishi Junji
Published: June 2009

A new and practical assay was developed using cultured FRTL-5 cells for simultaneous assessment of TS-ab and TSH-binding inhibitor immunoglobulin, allowing direct comparison of these two activities under the same conditions. Subsequent to the TS-ab assay in which extracellular cAMP concentration in Hanks' medium without NaCl was determined, [125I]bTSH in this medium was added to observe the ability of serum Ig to inhibit the binding of [125I]bTSH to FRTL-5 cells. We found a much higher specific binding of [125I]bTSH to FRTL-5 cells and a much greater inhibition of [125I]bTSH binding to the cells exposed to Graves' Ig in hypotonic NaCl-free than in NaCl containing Hanks' medium, indicating that the binding of both TSH and Graves' Ig to the TSH receptor was salt-sensitive. The inhibitory activity of [125I]bTSH binding to the cells was 0.2±4.6% (mean ±sd) in 45 normals. Inter-assay coefficients of variation in two positive controls with the mean values of 18.0 and 65.8% were 15.8 and 16.5%, respectively. Among 46 patients with untreated hyperthyroidism owing to Graves' disease, 45 (97.8%) were positive for TS-ab; 35 (76.1%) and 40 (87.0%) were positive for TSH-binding inhibitor in Ig assays using FRTL-5 cells and solubilized porcine thyroid membranes, respectively. TS-ab activities correlated less closely with TSH-binding inhibitory activities determined using FRTL-5 cells (r=0.576, p<0.001) than with those determined using porcine thyroid membranes (r=0.745, p<0.001). The correlation between TSH-binding inhibitory activities determined by the two methods, although statistically significant (r=0.537, p<0.001) was rather rough. Some patients clearly demonstrated discrepant results, suggesting the existence of heterogeneous populations of TSH receptor antibodies.
Pulsatile growth hormone release in Turner's syndrome and short normal children
Authors: Ghizzoni Lucia , Lamborghini Adima , Ziveri Mariangela , Volta Cecilia , Panza Costantino , Balestrazzi Paolo , Bernasconi Sergio
Published: June 2009

To determine whether the quantitative and qualitative aspects of GH secretion in girls with Turner's syndrome are similar to those of short-normal children we studied the 24-h GH secretion of 10 patients with Turner's syndrome and 9 short-normal children with comparable auxological features. GH profiles, obtained by 30-min sampling, were analysed by the Pulsar programme. The pulsatile GH release over the 24 h in Turner's syndrome was similar to that in normal children. However, when the GH release over the 12 day and night hours were separately analysed, only normal children showed a night-time increase in the sum of peak amplitudes. Moreover, patients with Turner's syndrome had significantly decreased number and frequency of peaks in the night-time compared with short children. In shortnormal children but not in Turner's syndrome, height velocity was related to the 24-h integrated concentration of GH, area under the curve over zero-line and over baseline, sum of peak areas, and amplitudes. Night-time GH area over zero-line and over baseline, mean peak amplitude, height, area, sum of peak areas, and amplitudes were positively correlated with height velocity in short children, whereas in Turner's syndrome height velocity was related to daytime parameters only. In conclusion, girls with Turner's syndrome have a discrete pattern of pulsatile GH release. However, the relation of GH secretion to growth, in these patients, is uncertain.
Epidermal growth factor and platelet-derived growth factor in blood in diabetes mellitus
Authors: Lev-Ran Arye , Hwang David L.
Published: June 2009

Epidermal and platelet-derived growth factors are potent mitogens for many types of cells, including smooth muscle cells. Epidermal growth factor in blood of humans is present both in platelets (as reflected in its serum level) and in plasma, the source(s) of which remains unknown. We assayed its level in 82 diabetic patients and 53 age-matched controls. In diabetes, epidermal growth factor level was increased in serum (191±43 vs 155±64 pmol/l, p = 0.0002 ) and plasma (53±9 vs 38±14 pmol/l, p<0.0001), without any difference between the patients with and without complications. Platelet-derived growth factor level was assayed only in serum of 19 patients with uncomplicated diabetes and found elevated (222±47) as compared with 13 controls (160±26 pmol/l), (p=0.0002). Type of diabetes, its duration, mode of therapy, control, presence of retinopathy or albuminuria (in case of epidermal growth factor), as well as C-peptide, age and sex did not correlate with epidermal or platelet-derived growth factor levels. Serum but not plasma epidermal and platelet-derived growth factor were negatively correlated with serum creatinine (correspondingly, r=−0.373, p=0.0008 and r= −0.564, p=0.0285). It is concluded that diabetes itself and not its complications cause increased levels of epidermal growth factor in plasma and serum and of platelet-derived growth factor in serum.
Insulin, glucagon, somatostatin, and thyrotropin-releasing hormone content and secretion by perifused fetal rat islets during culture
Authors: Vara E. , Idahl L.-Å. , Lindström P. , Sehlin J. , Tamarit-Rodriguez J.
Published: June 2009

In the neonatal period of the rat, pancreatic thyrotropin-releasing hormone content decreases and the sensitivity of insulin secretion to glucose increases. In adult rat islets, TRH inhibits glucose-induced insulin release. The aim of this study was to investigate whether a high TRH content and release can be part of the explanation for the functional immaturity of neonatal islets. For that purpose, we have measured the tissue content and the secretion of immunoreactive insulin, glucagon, somatostatin and TRH in islets from 21.5-day-old rat fetuses cultured for up to one week. Insulin, glucagon and somatostatin content increased during one week of culture in the presence of 11.1 mmol/l glucose. The TRH content decreased during culture, but did not equal adult values. Insulin, glucagon and somatostatin responses to glucose were present after one week of culture. Glucose had no effect on TRH release in cultured fetal islets, but inhibited TRH release in adult islets. We conclude that glucose can stimulate insulin secretion without inhibiting TRH release, but that a decrease in islet TRH content and a sensitization of TRH secretion to glucose may be important in the full maturation of fetal pancreatic islets.
Uninephrectomy inducing quantitative and qualitative changes in LH isoforms in the male rat
Authors: Ujihara Makoto , Nomura Kaoru , Toraya Shohzoh , Demura Hiroshi
Published: June 2009

Recent findings that LH stimulates renal growth have prompted us to examine whether LH exercises renotropic effects on the growing kidney following uninephrectomy. Intact (not castrated) male rats were used for sham uninephrectomy to induce surgical stress suppressing plasma LH and testosterone levels. Compared to sham surgery, uninephrectomy caused a transient 240% increase in plasma LH with a transient increase in plasma testosterone (80%) and in prostate weight on day 2. Although pituitary LH content did not change, chromatofocusing of pituitary extract revealed changed distribution patterns among seven LH isoforms, suggesting selective synthesis or secretion of LH isoforms. Castrated rats were then used so that surgical stress did not affect LH. Uninephrectomy caused sustained increases in plasma LH levels (60-110% increase) for up to six days. Three days after uninephrectomy, pituitary LH content increased significantly (30% increase) with a change in chromatofocusing profiles of LH isoforms. Plasma and pituitary FSH levels did not change. In summary, uninephrectomy changed LH isoforms quantitatively and qualitatively. These changes imply a change in gonadotropic and renotropic activities of LH after uninephrectomy.
Evidence for a long-term storage of calcitriol in a patient with 1-alpha hydroxylase deficiency and rickets
Authors: Rungby Jørgen , Mosekilde Leif , Poulsen Jørgen Hjelm
Published: June 2009

The ability of the human body to store substantiable amounts of not only inactive vitamin D metabolites but also the bioactive 1,25-hydroxylated metabolite was demonstrated in a patient suffering from renal hydroxylase deficiency.
Extrarenal receptor-effector-mechanisms for aldosterone: The sequence of effects on the cellular electrolyte transport in human lymphocytes and their implications for disorders of the water and electrolyte balances
Authors: Wehling Martin , Theisen Karl
Published: June 2009

High affinity aldosterone binding sites have not only been described in the classic target tissues such as the renal tubules, but also in non-classic target tissues such as the hippocampus, mammary gland, endothelial cells and, recently, human mononuclear leukocytes. An in vitro effect of aldosterone on intracellular sodium, potassium and calcium concentrations and cell volume was shown in human mononuclear leukocytes. In the absence of aldosterone, the intracellular Na+, K+ and Ca2+ concentrations and the cell volume decreased significantly, but remained constant when aldosterone (1.4 nmol/l) was added to the incubation medium. These effects of aldosterone were blocked by the aldosterone antagonist canrenone (140 nmol/l). The sodium/proton exchanger of the cell membrane could be identified as the primary target of the aldosterone action, possibly non-genomically mediated through membrane receptors. The clinical significance of this model was underlined by the demonstration of absent or a decreased number of mineralocorticoid receptors and the lack of electrolyte response to aldosterone in human mononuclear leukocytes of patients with pseudohypoaldosteronism and aldosteronism. Additionally, an abnormal effector mechanism could be demonstrated in human mononuclear leukocytes from essential hypertensives. These studies are the first to demonstrate the significance of extrarenal, nonepithelial mineralocorticoid receptors and the related effector mechanism in different disorders of the water and electrolyte balance in man.
Influence of danazol and goserelin on insulin and glucagon in non-obese women with endometriosis
Authors: Golland I. M. , Vaughan-Williams C. A. , Shalet S. M. , Laing I. , Elstein M.
Published: June 2009

To investigate the effects of medical treatment of endometriosis on concentrations of insulin and glucagon in comparison with those of androgens, 12 nonobese women with minimal endometriosis were randomly allocated to receive treatment with either danazol or the gonadotropin-releasing hormone analogue, goserelin. In subjects treated with danazol, mean (sd) summed serum insulin (1.08 (0.22) nmol/l pretreatment; 3.00 (1.50) nmol/l after treatment, p<0.05) and summed plasma glucagon (94 (21) pmol/l pretreatment; 238 (113) pmol/l after treatment, p<0.05) responses to oral glucose administration increased significantly, but remained unchanged in subjects treated with goserelin. In the danazol-treated group, the mean free testosterone index increased from 3.3 (1.6) to 13.3 (4.2) (p<0.01), but there was no correlation between either glucagon or insulin and free testosterone index. In the goserelin-treated subjects, however, there was no change in mean free testosterone indices (pretreatment 3.6 (1.0), post-treatment 3.9 (1.8). Thus, the increase in free testosterone index induced by danazol treatment is not responsible for the concomitant development of hyperinsulinaemia and hyperglucagonaemia.
Depression of calcium pump activity in renal cortex of vitamin D-deficient rats with secondary hyperparathyroidism
Authors: Tsukamoto Yusuke , Tamura Teiichi , Saitoh Michiyo , Takita Yumiko , Nakano Toshiaki
Published: June 2009

To examine the hormonal regulation of the ATP-dependent Ca2+ pump in the kidneys, the ATP-dependent Ca2+ uptake by the basolateral membrane vesicles in the renal cortex was measured using radioactive calcium (45Ca2+) in rats with vitamin D deficiency or rats undergoing thyroparathyroidectomy. The Vmax of the Ca2+ pump activity was increased not only by administering calcitriol, but also by normalizing the serum calcium level in vitamin D-deficient rats. PTH suppressed the Ca2+ pump activity in normocalcemic vitamin D-deficient rats. Thyroparathyroidectomy did not affect the Ca2+ pump activity in the kidneys of normal rats. It was concluded that the ATP-dependent Ca2+ pump activity was depressed by secondary hyperparathyroidism in vitamin D-deficient rats.
Thyroid hormone excess stimulates the synthesis of proteoglycan in human skin fibroblasts in culture
Authors: Shishiba Yoshimasa , Takeuchi Yasuhiro , Yokoi Noriko , Ozawa Yasunori , Shimizu Taeko
Published: June 2009

We previously demonstrated that proteoglycan accumulated in the affected skin of circumscribed pretibial myxedema of Graves' disease. As an underlying mechanism responsible for the accumulation, we sought to determine whether excess thyroid hormone was partially responsible for the increase in proteoglycan synthesis. Human skin fibroblasts were cultured in Ham's F-10 medium containing 1% Nutridoma with graded doses of T3 (0.184 × 10−9 to 46 × 10−9 mol/l) and were labelled with [35S]sulphate and [3H]glucosamine. Proteoglycans were purified by Sephadex G-50, Q-Sepharose chromatography with NaCl-gradient and Sepharose CL-6B chromatography. 35S and 3H incorporated into dermatan sulphate proteoglycan and heparan sulphate proteoglycan and 3H incorporated into hyaluronan were measured. 35S and 3H incorporation into dermatan sulphate proteoglycan was minimum at a T3 concentration of 0.184 × 10−9 mol/l, and increased with increasing doses of T3 up to 46 × 10−9 mol/l. 35S and 3H incorporation into heparan sulphate proteoglycan also increased with increasingdoses of T3. 3H incorporation into hyaluronan was not influenced at all by T3. The increased incorporation of 35S into proteoglycan in high-T3 culture reflects the increased synthesis of proteoglycan because 1. the extent of sulphation of disaccharides examined by thin-layer chromatography was not altered by T3; 2. the specific activity of [35S]sulphate was not influenced by T3, and 3. T3 did not decrease the degradation rate of cell-associated proteoglycan.
Hepatic drug metabolism is increased in poorly controlled insulin-dependent diabetes mellitus
Authors: Goldstein Steven , Simpson Anna , Saenger Paul
Published: June 2009

In addition to increased glycosylation of hemoglobin, abnormalities of other heme proteins such as cytochrome P-450 might also occur in patients with insulin-dependent diabetes mellitus. Antipyrine is a useful marker drug for cytochrome P-450 dependent hepatic drug metabolism. Antipyrine kinetics and urinary excretion of antipyrine metabolites were measured in 14 patients with insulin-dependent diabetes mellitus in poor metabolic control. Improvement in diabetic control in 9 patients, as measured by more normal HbA1 values, led to normalization of plasma antipyrine half-time (t½) and metabolism: the mean antipyrine t½ slowed from 4.7±0.2 (sem) initially to 7.8±0.3 h in these 9 patients and was thus nearly identical to that of normal subjects 8.6±1.0. Antipyrine plasma clearance improved in the 9 diabetic patients whose diabetic control improved. The apparent volume of distribution was normal on both occasions in the diabetic patients. These findings provide a new argument for tight metabolic control in patients with insulin-dependent diabetes mellitus.
Correlation between amniotic levels of α-MSH, ACTH and β-endorphin in late gestation and labour in normal and complicated pregnancies
Authors: Mauri Alessandro , Serri Francesco , Caminiti Francesco , Mancuso Salvatore , Fratta Walter , Gessa Gian Luigi , Argiolas Antonio
Published: June 2009

α-MSH, ACTH and β-endorphin were measured by radioimmunoassay in samples of amniotic fluid collected from the 32nd to the 38th gestational week and at labour from normal pregnancies and pregnancies complicated by gestosis. In normal pregnancies, the concentration of α-MSH, ACTH and β-endorphin remained relatively constant during the last 7 gestational weeks, but increased at labour above the values of the 38th week by 88, 143 and 96%, respectively. A positive correlation between β-endorphin and α-MSH (r=0.92) or ACTH (r=0.76) levels was found when labour values were considered in the regression analysis. In contrast, when labour values were excluded, only a poor positive correlation between β-endorphin and α-MSH (r=0.52) was found. In complicated pregnancies, α-MSH and ACTH concentrations were similar to those found in normal pregnancies; on the other hand, the level of β-endorphin, was found to be 130% higher than normal. As in normal pregnancies, α-MSH, ACTH and β-endorphin levels increased at labour, but only by 46, 44 and 23%, respectively. In contrast to in normal pregnancies, the correlation between β-endorphin and α-MSH or ACTH was not significantly modified by labour values. The present results confirm and extend previous studies showing that β-endorphin may be considered a marker of fetal distress and that the fetal pituitary is capable of reacting to stressful stimuli in normal and suffering fetuses.