bluuebunny/crossref_metadata_2025 huggingface dataset:
Ventralis Intermedius Thalamotomy Can Succeed when Ventralis Intermedius Thalamic Stimulation Fails: Report of 2 Cases for Tremor
Authors: Giller Cole A. , Dewey Jr. Richard B.
Published: April 2003

In 2 patients with essential tremor, thalamotomy in the ventralis intermedius (VIM) provided lasting tremor relief after thalamic stimulation of the VIM failed. These cases illustrate that the effects of deep brain stimulation might not be those of simple inhibition, and that thalamotomy should be considered when deep brain stimulation does not succeed.
Prolonged Neurogenesis during Early Development of Gonadotropin-Releasing Hormone Neurones in Sheep (Ovis aries): In vivo and in vitro Studies
Authors: Bruneau G. , Izvolskaia M. , Ugrumov M. , Tillet Y. , Duittoz A.H.
Published: April 2003

Gonadotropin-releasing hormone (GnRH) neurons involved in controlling the reproductive function in vertebrates are derived from the olfactory placode. However, in the sheep and the rat species, GnRH-immunoreactive (GnRH-IR) neurons could not be detected in the olfactory region during the earliest phase of GnRH system development. Using in situ hybridization (ISH) and immunohistochemistry (IHC) in sheep embryos ranging from 26 to 53 days’ gestational age (G26–G53), the present work confirmed that GnRH expression could not be detected during the earliest steps of migration. The first ISH+ cells were detected in the nasal septum and at the entrance of the telencephalon at G33 stage. [3H]-thymidine pulses applied to in vitro olfactory explant cultures showed that GnRH neuron precursor cells have an extended multiplication period corresponding to G26–G36 before entering the neuronal differentiation process. Therefore, the lack of GnRH neuron detection during the early phase of development in the sheep compared to the mouse and other vertebrates represents a major difference in the early development of GnRH neurons. In the mouse, GnRH neuron precursors have a limited multiplication period in the vomeronasal pit and only postmitotic neurons start migration, whereas in the sheep embryo, the multiplication period is extended to about 10 days as demonstrated in olfactory explant cultures.
Orexin-B Augments Voltage-Gated L-Type Ca2+ Current via Protein Kinase C-Mediated Signalling Pathway in Ovine Somatotropes
Authors: Xu Ruwei , Roh Sang-Gun , Gong Changhong , Hernandez Maria , Ueta Yoichi , Chen Chen
Published: April 2003

Orexins, orexigenic neuropeptides, are secreted from lateral hypothalamus and orexin receptors are expressed in the pituitary. Since growth hormone (GH) secreted from pituitary is integrally linked to energy homeostasis and metabolism, we studied the effect of orexin-B on voltage-gated Ca2+ currents and the related signalling mechanisms in primary cultured ovine somatotropes using whole-cell patch-clamp techniques. With a bath solution containing TEA-Cl (40 mM) and Tetrodotoxin (TTX) (1 µM), three subtypes of Ca2+ currents, namely the long-lasting (L), transient (T), and N currents, were isolated using different holding potentials (–80 and –30 mV) in combination with specific Ca2+ channel blockers (nifedipine and ω-conotoxin). About 75% of the total current amplitude was contributed by the L current, whereas the N and T currents accounted for the rest. Orexin-B (1–100 nM) dose-dependently and reversibly increased only the L current up to approximately 125% of the control value within 4–5 min. Neither a specific protein kinase A (PKA) blocker (H89, 1 µM) nor an inhibitory peptide (PKI, 10 µM) had any effect on the increase in L current by orexin-B. The orexin-B-induced increase in the L current was abolished by concurrent treatment with calphostin C (Cal-C, 100 nM), protein kinase C (PKC) inhibitory peptide (PKC19–36, 1 µM), or by pretreatment with phorbol-12,13-dibutyrate (PDBu) (0.5 µM) for 16 h (a downregulator of PKC). Orexin-B also increased in vitro GH secretion in a dose-dependent manner. We conclude that orexin-B increases the L-type Ca2+ current and GH secretion through orexin receptors and PKC-mediated signalling pathways in ovine somatotropes.
Biology of Congenital Obstructive Nephropathy
Authors: Liapis Helen
Published: April 2003

Congenital obstructive nephropathy is a common disease affecting fetuses and young children. The kidney shows profound morphologic and functional changes. The physiologic developmental kidney program is disturbed in the most advanced cases, arguing for altered temporal/spatial expression of genes which control normal nephrogenesis. Major regulators of mesenchymal-epithelial transformation and collecting duct and tubular development such as WT1 and Sall1 are decreased with obstruction. Additional candidate genes include GDNF/cRET, LIM1 and Pax2. Excessive apoptosis is an undisputed mechanism in these processes, mediated by decreased expression of apoptosis inhibiting genes (Bcl-2, HGF, IGF, BMP7), and overexpression of pro-apoptotic genes like Bax and TGF-β. Renin and AT2R implicated in renal vascular development are decreased. Numerous extracellular matrix genes including Matrilysin are altered. The emerging theories of the biology of congenital obstructive nephropathy suggest new targets for therapeutic interventions with profound implications for these children.
Homosexual Delusional Jealousy in Two Heterosexual Women
Authors: Livianos Aldana Lorenzo , San Miguel Pilar Sierra , Rojo Moreno Luis , Martinez Raga José
Published: April 2003

The present paper focuses on two patients suffering from delusional jealousy with an uncommon feature. Both cases are women who developed a homosexual delusional jealousy, that is, ‘the phantom other’ is a person of the same gender as the individual supposedly having an affair. The discussion centres on the possible sociological aspects and changes in the ‘Zeitgeist’ that may have favoured the onset of the two reported cases.
Interpersonal Aspects of the Syndromes of Schizophrenia
Authors: Shean Glenn , Abel Eva , DeSalvo Carla
Published: April 2003

Raters listened to interviews with schizophrenic patients and rated each participant using Wiggins’s Interpersonal Adjective Checklist-Revised, a measure of interpersonal behavior. It was predicted that three symptom dimensions (disorganization, psychoticism and negative symptoms) would be associated with unique patterns of interpersonal behavior. Results indicated that symptoms of psychoticism (systematized delusions and auditory hallucinations) were rated as evidencing Arrogant-Calculating characteristics. Negative symptoms were associated with Unassured-Unassuming and Aloof-Introverted patterns. Symptoms of disorganization were associated with Quarrelsome behavior. Increased knowledge of the interpersonal styles associated with different subsyndromal patterns of schizophrenic symptoms, and the reactions they are likely to elicit in others, can provide a useful framework for the design of social-cognitive rehabilitation programs.
Mental State Examination: The Elicitation of Symptoms
Authors: Jacob K.S.
Published: April 2003

The general rules for elicitation of symptoms during the Mental State Examination (MSE) are not usually emphasized during the training of mental health professionals. This paper discusses principles which can be used to elicit and establish symptoms. The issues include the gold standard, demarcation of abnormalities, screening and confirmation, changes in population characteristics, prevalence and predictive values. The Bayesian framework is elaborated. The principles of elicitation should be emphasised during the training so that trainees have a more rational basis for the use of the MSE.
Induced Delusional Disorder
Authors: Wehmeier Peter M. , Barth Nikolaus , Remschmidt Helmut
Published: April 2003

Induced delusional disorder (or shared paranoid disorder), also known as folie à deux, is a fairly uncommon disturbance characterized by the presence of similar psychotic symptoms in two or more individuals. Most often the symptoms are delusional. Usually the ‘primary’ case, i.e. the individual who first develops psychotic symptoms, can be distinguished from one or more ‘secondary’ cases, in whom the symptoms are induced. We discuss the concept of shared paranoid disorder and consider various aetiological, clinical and diagnostic issues related to the disturbance. We also describe a case of folie à famille, this condition being a type of shared paranoid disorder. The case involves a couple and their 12-year-old son. The boy’s father is the ‘primary’ case, whilst the boy and his mother are both ‘secondary’ cases. The boy was admitted to our child and adolescent psychiatric unit for in-patient treatment. Treatment success was moderate in terms of improving the features of folie à famille in the three individuals involved.
Old Wine in New Bottles?
Authors: Stompe T. , Ortwein-Swoboda G. , Ritter K. , Schanda H.
Published: April 2003

A number of recent case reports published during the last 20 years described a quick inclusion of new technologies and cultural innovations into schizophrenic delusions which led many of the authors to the conclusion that the ‘Zeitgeist’ is creating new delusional contents. On the other hand, long-term comparisons and comparative transcultural studies on delusions showed, despite a certain degree of variability, a stability of delusional themes over longer periods of time. Combining anthropological and historical theories of the development of societies with a differentiated psychopathological approach (Klosterkötter’s three-stage model of the formation of schizophrenic delusions), we were able to resolve the problem of the ostensibly divergent results: there are only a few themes of extraordinary anthropological importance for the organization of human relationships which can be found in every epoch and in different cultures (persecution, grandiosity, guilt, religion, hypochondria, jealousy, and love). With the exception of persecution and grandiosity, these themes showed a certain variability over time and between cultures. The ‘new’ themes, referring to the development of modern technology and the rapid changes of ‘cultural patterns’ turned out to be only the shaping of the basic delusional themes on the 3rd stage of Klosterkötter’s phase model (concretization).
Cognitive Inhibition and Thought Disorder in Schizophrenia
Authors: Roesch-Ely Daniela , Spitzer Manfred , Weisbrod Matthias
Published: April 2003

In schizophrenia, inhibitory control is reported to be disturbed and has been associated with formal thought disorder (TD). The negative priming task (NP) is used as a measure for inhibition; however, controversial results are found in the literature. The aim of this study was to evaluate cognitive inhibition in schizophrenia and TD. Additionally, the influence of the course of disease and of medication were evaluated. The NP was used to compare TD patients (n = 17) with non-TD (n = 19) and healthy controls (n = 21). Results showed similar performance among TD and non-TD patients, and controls. No influence of the course of disease or medication was found. Our results are in line with recent studies, where patients, irrespective of TD, show normal performance in the NP.
Cardiovascular Manifestations of Thyroid Disease
Authors: Albrecht III Charles R. , Gambert Steven R.
Published: April 2003

Abnormalities of thyroid function have significant effects on the cardiovascular system. This review discusses the role of thyroid hormone in regulating cardiac function under normal circumstances as well as the cardiovascular manifestations of hypo- and hyperthyroidism.
Logistics of Primary Angioplasty
Authors: Ribichini Flavio , Ferrero Valeria , Vassanelli Corrado
Published: April 2003

Aims: After many years of debate, primary angioplasty has emerged as the best reperfusion treatment for acute myocardial infarction (AMI). However, the scarce availability of qualified invasive facilities remains the major limitation of this strategy compared to the simple intravenous administration of effective lytic agents. Methods: To enlarge the availability of invasive centers where patients with AMI could be promptly treated with primary angioplasty two lines of action may be pursued; the first is the ‘up-grading’ of low-volume interventional or diagnostic laboratories that do not perform emergency interventions on a regular basis; the second is the creation of a transportation network that enables pre-hospital fibrinolysis and/or the referral of patients from non-invasive centers to high-volume tertiary structures committed to the treatment of AMI at any time. Results: Recent data obtained from randomized studies support both alternatives. In fact, pre-hospital fibrinolysis and transportation or patient transportation without previous fibrinolysis are safe and offer better clinical outcome compared to fibrinolysis started in hospital. Besides, primary angioplasty can also be performed in selected community centers intensively trained that, performing large work volumes, can achieve superior results compared to fibrinolysis started in hospital. Conclusions: The advantages and shortcomings of these two alternatives are commented on in this article
Connections of the Pallial Telencephalon in the Senegal Bichir, Polypterus
Authors: Holmes Preston H. , Northcutt R. Glenn
Published: April 2003

The connections of the dorsal telencephalon (pallium) of the Senegal bichir (Polypterus senegalus) were investigated in order to test the hypothesis that the simple everted pallium of polypterid fishes is directly comparable to the evaginated pallium of most vertebrates. Neuroanatomical tracers (DiI or biotinylinated dextran amines) were injected into the three traditionally recognized divisions of the bichir pallium to determine their afferent and efferent connections. The connections were corroborated with injections into regions identified as projecting to, or receiving input from, one or more pallial divisions. The results suggest that the bichir pallium consists not of three, but only two primary divisions: a dorsomedial one and a dorsolateral one. This reinterpretation refutes the hypothesis of a direct one-to-one comparison with the tripartite pallium of most vertebrates. Homologues of the bichir dorsomedial and dorsolateral pallium are recognized in the lateral and medial pallium of anuran amphibians, respectively. The pallium of bichirs is compared to that of derived ray-finned fishes as a link between derived ray-finned fishes and other vertebrates. The available information on the connections of the pallium of teleosts suggests that only the olfactory recipient (pars posterior) of the pallium can be directly compared to bichirs and amphibians and that the remaining divisions of the pallium in teleosts are uniquely derived features of the teleost telencephalon.
Assessing Behavior in Extinct Animals: Was Smilodon Social?
Authors: McCall Sherman , Naples Virginia , Martin Larry
Published: April 2003

It has been suggested that saber-tooth species such as Smilodon fatalis were social because partially healed skeletal injuries were found at Rancho La Brea, California. This conclusion assumes injured animals would die without help. This paper will rebut assertions of sociality. First, cats use metabolic reserves to heal quickly without feeding. Second, dehydration is a more profound limitation than starvation as prey carcasses only provide a quarter of necessary water. Injured animals must be mobile enough to find water or die of dehydration. Their presence in a tar pit also strongly suggests locomotion. Finally, the relatively small brain found in Smilodon is not consistent with sociality. Another argument for sociality has been the large ratio of Smilodon to other species in the La Brea tar pits. However, the remains of a non-social species, the Golden eagle (Aquila chrysaetus), are about as common as Smilodon. Contrariwise, the highly social grey wolf (Canis lupus) and coyote (Canis latrans) are extremely rare. Available evidence does not support sociality in Smilodon.
Parathyroid Hormone Has a Prosclerotic Effect on Vascular Smooth Muscle Cells
Authors: Perkovic Vlado , Hewitson Timothy D. , Kelynack Kristen J. , Martic Marina , Tait Melanie G. , Becker Gavin J.
Published: April 2003

Although accelerated atherosclerosis and arteriosclerosis are common in patients with renal failure, the pathogenesis of these changes is poorly understood. Parathyroid hormone (PTH) levels are elevated in renal failure, and have been linked to uraemic vascular changes in some studies. We examined the in vitro effects of increasing doses of the 1–34 fragment of PTH on human aortic vascular smooth muscle cells (VSMCs). Factors examined were: (1) collagen production using tritiated hydroxyproline incorporation and transcription of procollagen α1(I) mRNA; (2) change in the surface area of collagen I lattices; (3) mRNA transcription of the collagen binding protein β1 integrin; (4) proliferation using tritiated thymidine incorporation, and (5) methyl tetrazolium salt conversion to estimate live cell number after 5 days’ exposure to PTH. PTH at a concentration of 200 pmol/l increased total collagen synthesis (188 ± 25% of control, p < 0.01) as well as transcription of procollagen α1(I) mRNA (136 ± 11% of control, p < 0.005). PTH also increased reorganisation of collagen I lattices (surface area 47 ± 8% of well for control vs. 35.7 ± 2.5 and 34.3 ± 3.0% for PTH 100 and 200 pmol/l, respectively, p = 0.02) and upregulated β1 integrin mRNA expression (160 ± 20% of control at PTH concentration of 200 pmol/l, p < 0.05). PTH had no effect on VSMC proliferation or number at doses up to 200 pmol/l. In conclusion, PTH increases production and reorganisation of collagen by VSMCs in vitro. It is possible that more aggressive control of hyperparathyroidism in patients with renal failure may help to reduce the burden of cardiovascular disease in this patient population.
Castleman’s Disease in a Child Presenting with a Partly Mineralized Solitary Meningeal Mass
Authors: Sotrel Ana , Castellano-Sanchez Amilcar A. , Prusmack Chad , Birchansky Sherri , Brathwaite Carole , Ragheb John
Published: April 2003

We report a case of solitary intracranial childhood Castleman’s disease (CD) presenting with a sudden onset of partial seizures due to a meningeal and cortical mass lesion. The patient was a previously healthy 8-year-old girl who developed a new onset of simple partial seizures with motor signs. On physical examination, she was neurologically intact. Other findings included low-grade fever, mild microcytic anemia and lymphopenia. Magnetic resonance imaging (MRI) of the brain revealed a left posterior parietal, partly mineralized, contrast-enhancing meningeal mass with cortical invasion and adjacent white matter edema. A complete surgical resection of the dural-based component and a subtotal resection of the adherent, invasive cortical lesion were performed. Pathohistology and flow cytometry of the dural-based lesion disclosed a hyaline-vascular type of CD with striking proliferation of polyclonal B lymphocytes, scattered plasma cells and extensive multifocal cortical mineralization. At the 6-month follow-up, the patient was seizure free on antiepileptics and had returned to normal daily activities. MRI showed no residual lesion, and a workup for systemic disease was negative.
Craniocervical Anomalies in Dubowitz Syndrome
Authors: Swartz Karin R. , Resnick Daniel K. , Iskandar Bermans J. , Wargowski David , Brockmeyer Douglas , Opitz John M.
Published: April 2003

Dubowitz syndrome is a disorder involving craniofacial abnormalities, growth retardation and mental retardation. Approximately 142 cases have been reported, with various associated other anomalies. These include cardiovascular, urogenital and endocrine abnormalities, as well as a predisposition to infections and hematological malignancies. Scoliosis has been described in association with this syndrome, as have isolated vertebral abnormalities. There has, however, been no description of craniocervical abnormalities. We describe three Dubowitz patients with significant craniocervical abnormalities.
Bilateral Carpal Tunnel Syndrome with Type 1 Diabetes mellitus in Childhood
Authors: Kayali Hakan , Kahraman Serdar , Sirin Sait , Bedük Altay , Timurkaynak Erdener
Published: April 2003

The differences between diabetic mono- or polyneuropathy and entrapment neuropathy are most important with respect to choosing treatment alternatives in pediatric patients. A 7-year-old girl with type 1 diabetes mellitus was admitted to our clinic with a complaint of bilateral weakness in her hands. Her clinical findings and electromyography study revealed an entrapment neuropathy of the median nerve at the wrist. She underwent operation by open carpal tunnel release. All symptoms resolved within 6 months after the operation. Carpal tunnel syndrome, especially bilateral, is very rare in childhood and it can be treated surgically.
Occipital Condyle Fractures in Children
Authors: Momjian S. , Dehdashti A.R. , Kehrli P. , May D. , Rilliet B.
Published: April 2003

Occipital condyle fractures (OCF) are seldom described in children, with only 14 cases reported in the literature. We report the observation of a 13-year-old child in whom such a fracture was diagnosed. A review of the paediatric cases allowed us to identify the clinical features of OCF in children. The average age was found to be 10 years, and the causative traumatism was most often related to road traffic or sporting accidents with associated head injury. The level of consciousness was depressed in 67% of the cases, and in 53%, an injury to the cranial nerves, brain stem or high spinal cord was present. Neck pain with reduction of head mobility was reported in 27% of the cases. Treatment was generally conservative, i.e. a hard collar or halo vest for an average of 8 weeks. The course was favourable with respect to osseous consolidation, mobility and pain. On the other hand, the neurological deficits improved, but sequelae remained. Early diagnosis and treatment is mandatory since the secondary displacement of fractured fragments can injure the cranial nerves in a delayed fashion or even be fatal due to compression of the brain stem.
Damage Mechanisms in Duplex Treated Hot Work Tool Steel under Thermal Cycling
Authors: Pellizzari M. , Molinari A. , Straffelini G.
Published: April 2003

Duplex treatments are becoming increasingly interesting in several technological applications through which complex forms of stresses act during service. In pressure die casting, for example, corrosion and erosion by molten metal and oxidation contribute, together with thermal fatigue, to excessive degradation of the dies and inserts. While the benefits introduced by combining nitriding and PVD coating have been assessed in counteracting soldering and wear problems, the resistance of such duplex systems with respect to thermal fatigue has not yet been established.

In this work, the role of plasma nitriding, PVD coating (CrN, ZrN), and duplex treatment in counteracting thermal cracking, i.e. heat checking, of hot work tool steel is considered. Thermal fatigue tests carried out on a laboratory scale, highlight the negative role of coatings, although this result has to be partially ascribed to an unsuitable prenitriding treatment and heavy oxidation.
Nitriding Response of Chromium Containing Ferritic Steels on Plasma Immersion Ion Implantation at Elevated Temperature
Authors: Blawert C. , Mordike B. L. , Rensch U. , Schreiber G. , Oettel H.
Published: April 2003

The result of nitriding ferritic steels using a PI3 treatment depends strongly on the composition of the steel. For chromium containing steels, an expanded ferrite phase was found for higher chromium contents (about 3.6%Cr) under certain treatment conditions. Standard metallography did not reveal any precipitation and the treated surface layer possessed a uniform microstructure. The expanded ferrite phase exhibits high hardness and thus good wear resistance.
Numerical Modelling of Motion and Heating of Particles during Plasma Spraying
Authors: Liu B. , Zhang T. , Bao Y. , Gawne D. T.
Published: April 2003

A theoretical model based on a CFD (computational fluid dynamics) methodology has been developed to simulate the motion and heating of particles in a plasma jet during plasma spraying. The particle motion and heat transfer equations are solved semianalytically using a prediction-correction method, taking into account phase changes during heating. The computational model is verified by experimental measurements and by comparison with experimental data in the literature. The results show that the relative motion between particles and the plasma jet has a major influence on particle heating through its influence on the heat transfer coefficient. The computational model can be used to predict the velocity, temperature, degree of melting, and trajectory of feedstock particles during practical plasma spraying.
Comparison studies on properties of nitrogen and carbon S phase on low temperature plasma alloyed AISI 316 stainless steel
Authors: Thaiwatthana S. , Li X. Y. , Dong H. , Bell T.
Published: April 2003

S phase layers produced on AISI 316 stainless steel by low temperature plasma nitriding and plasma carburising were examined in order to investigate their mechanical and chemical properties. Cylindrical disc specimens were used for testing hardness, pin on disc wear and electrochemical corrosion. Toroidal specimens were used for the fatigue and fretting fatigue tests. Both plasma nitriding and carburising processes created S phase layers on the surface of AISI 316 and greatly improved the steel's tribological properties. SEM showed that more precipitation of nitrogen occurred in the plasma nitrided specimens and GDS revealed that the nitrogen in the nitriding specimens did not penetrate as far into the substrate as the carbon in the carburising specimens. This is due to the nitrogen bonding easily with chromium in the surface layer which obstructs the diffusion of nitrogen into the substrate. The hardness tests showed that the nitriding layer was harder than the carburised layer but was more brittle and did not extend far into the substrate whereas the hardness of the carburised layer reduced gradually to a depth of 10 μm. The nitrided layer did better in the abrasion tests whereas the carburising layer performed better in the fatigue tests. The importance of these discoveries is discussed.
Centrally Administered Tuberoinfundibular Peptide of 39 Residues Inhibits Arginine Vasopressin Release in Conscious Rats
Authors: Sugimura Yoshihisa , Murase Takashi , Ishizaki Seiji , Tachikawa Kazushige , Arima Hiroshi , Miura Yoshitaka , Usdin Ted B. , Oiso Yutaka
Published: April 2003

Tuberoinfundibular peptide of 39 residues (TIP39) is a recently discovered neuropeptide identified on the basis of its ability to activate the PTH2 receptor, and it is thought to be the brain PTH2 receptor’s endogenous ligand. The PTH2 receptor is highly expressed in the hypothalamus, suggesting a role in the modulation of neuroendocrinological functions. PTHrP, which also belongs to the PTH-related peptides family, stimulates arginine vasopressin (AVP) release. In the present study, therefore, we investigated the effect of centrally administered TIP39 on AVP release in conscious rats. Intracerebroventricular administration of TIP39 (10–500 pmol/rat) significantly suppressed the plasma AVP concentration in dehydrated rats, and the maximum effect was obtained 5 min after administration (dehydration with 100 pmol/rat TIP39, 4.32 ± 1.17 pg/ml; vs. control, 8.21 ± 0.70 pg/ml). The plasma AVP increase in response to either hyperosmolality [ip injection of hypertonic saline (HS), 600 mosmol/kg] or hypovolemia [ip injection of polyethylene glycol (PEG)] was also significantly attenuated by an intracerebroventricular injection of TIP39 (HS with 100 pmol/rat TIP39, 2.65 ± 0.52 pg/ml; vs. HS alone, 4.69 ± 0.80 pg/ml; PEG with 100 pmol/rat TIP39, 4.10 ± 0.79 pg/ml; vs. PEG alone, 6.19 ± 0.34 pg/ml). Treatment with naloxone [1.5 mg/rat, sc injection], a nonselective opioid receptor antagonist, significantly reversed the inhibitory effects of TIP39 on AVP release. These results suggest that central TIP39 plays an inhibitory role in the osmoregulation and baroregulation of AVP release and that intrinsic opioid systems are involved in its mechanism.
Arcuate Nucleus-Specific Leptin Receptor Gene Therapy Attenuates the Obesity Phenotype of Koletsky (fak/fak) Rats
Authors: Morton Gregory J. , Niswender Kevin D. , Rhodes Christopher J. , Myers Martin G. , Blevins James E. , Baskin Denis G. , Schwartz Michael W.
Published: April 2003

Leptin signaling in the hypothalamic arcuate nucleus (ARC) is hypothesized to play an important role in energy homeostasis. To investigate whether leptin signaling limited to this brain area is sufficient to reduce food intake and body weight, we used adenoviral gene therapy to express the signaling isoform of the leptin receptor, leprb, in the ARC of leptin receptor-deficient Koletsky (fak/fak) rats. Successful expression of adenovirus containing leprb (Ad-leprb) selectively in the ARC was documented by in situ hybridization. Using real-time PCR, we further demonstrated that bilateral microinjection of Ad-leprb into the ARC restored low hypothalamic levels of leprb mRNA to values approximating those of wild-type (Fak/Fak) controls. Restored leptin receptor expression in the ARC reduced both mean daily food intake (by 13%) and body weight gain (by 33%) and increased hypothalamic proopiomelanocortin mRNA by 65% while decreasing neuropeptide Y mRNA levels by 30%, relative to fak/fak rats injected with a control adenovirus (Ad-lacZ) (P < 0.05 for each comparison). In contrast, Ad-leprb delivery to either the lateral hypothalamic area of fak/fak rats or to the ARC of wild-type Fak/Fak rats had no effect on any of these parameters. These findings collectively support the hypothesis that leptin receptor signaling in the ARC is sufficient to mediate major effects of leptin on long-term energy homeostasis. Adenoviral gene therapy is thus a viable strategy with which to study the physiological importance of specific molecules acting in discrete brain areas.
Phosphorylation of Insulin-Like Growth Factor Binding Protein-3 by Deoxyribonucleic Acid-Dependent Protein Kinase Reduces Ligand Binding and Enhances Nuclear Accumulation
Authors: Schedlich Lynette J. , Nilsen Trine , John Anna P. , Jans David A. , Baxter Robert C.
Published: April 2003

The IGF binding proteins (IGFBPs) regulate the mitogenic effects of IGFs in the extracellular environment. Several members of this family, including IGFBP-3, also appear to have IGF-independent effects on cell function. For IGFBP-3 and IGFBP-5, both of which are translocated to the cell nuclei, these effects may be related to their putative nuclear actions. Because reversible phosphorylation is an important mechanism for controlling nuclear protein import, we have examined the effect of phosphorylating IGFBP-3 with a number of serine/threonine protein kinases on its nuclear import. Phosphorylation of IGFBP-3 by the double-stranded DNA-dependent protein kinase (DNA-PK) increased both the nuclear import of IGFBP-3 and the binding of IGFBP-3 to components within the nucleus compared with nonphosphorylated IGFBP-3. However, there was no difference in the binding of the nuclear transport factor, importin β, to nonphosphorylated and phosphorylated IGFBP-3. The ability of the DNA-PK phosphoform of IGFBP-3 to bind IGFs was severely attenuated, and in contrast to nonphosphorylated IGFBP-3, the DNA-PK phosphoform was unable to transport IGF-I to the nucleus. Furthermore, IGFBP-3 was phosphorylated by DNA-PK when complexed to IGF-I causing the phosphoform to release IGF-I. Together, these results suggest that when IGF-I is cotransported into the nucleus by IGFBP-3, phosphorylation of IGFBP-3 by nuclear DNA-PK provides a means for releasing bound IGF-I and creating a phosphoform of IGFBP-3 with increased affinity for nuclear components.
Regulation of Hepatic GLUT8 Expression in Normal and Diabetic Models
Authors: Gorovits Naira , Cui Lingguang , Busik Julia V. , Ranalletta Mollie , de-Mouzon Sylvie Hauguel , Charron Maureen J.
Published: April 2003

GLUT8 is a novel glucose transporter protein that is widely distributed in tissues including liver, a central organ of regulation of glucose homeostasis. The purpose of the current study was to investigate expression and regulation of hepatic GLUT8 mRNA and protein. Therefore, Northern and immunoblot analysis, semiquantitative RT-PCR, and immunofluorescence microscopy were performed using mouse livers at different stages of embryonic and postnatal development and in type 1 (streprozotocin treated) and type 2 (GLUT4 heterozygous) diabetes. GLUT8 mRNA and protein expression in embryonic liver was differentially regulated depending on the prenatal and postnatal developmental stage of the mice. Immunofluorescence microscopy of liver from wild-type mice demonstrated the highest levels of GLUT8 protein in perivenous hepatocytes pointing to its role in regulation of glycolytic flux. In diabetic scenarios, GLUT8 mRNA levels were correlated with circulating insulin; specifically, GLUT8 mRNA decreased in a type 1 diabetes model and increased in a type 2 diabetes model, suggesting a regulatory role for insulin in GLUT8 mRNA expression. While up-regulation of GLUT8 protein occurred in both models of diabetes, only in streptozotocin diabetic livers was GLUT8 zonation altered. These data demonstrate that GLUT8 mRNA and protein are differentially regulated in liver in response to physiologic and pathologic (diabetes) milieu and suggests that GLUT8 is intimately linked to glucose homeostasis.
Osteopontin Deficiency Induces Parathyroid Hormone Enhancement of Cortical Bone Formation
Authors: Kitahara Keiichiro , Ishijima Muneaki , Rittling Susan R. , Tsuji Kunikazu , Kurosawa Hisashi , Nifuji Akira , Denhardt David T. , Noda Masaki
Published: April 2003

Intermittent PTH treatment increases cancellous bone mass in osteoporosis patients; however, it reveals diverse effects on cortical bone mass. Underlying molecular mechanisms for anabolic PTH actions are largely unknown. Because PTH regulates expression of osteopontin (OPN) in osteoblasts, OPN could be one of the targets of PTH in bone. Therefore, we examined the role of OPN in the PTH actions in bone. Intermittent PTH treatment neither altered whole long-bone bone mineral density nor changed cortical bone mass in wild-type 129 mice, although it enhanced cancellous bone volume as reported previously. In contrast, OPN deficiency induced PTH enhancement of whole-bone bone mineral density as well as cortical bone mass. Strikingly, although PTH suppressed periosteal bone formation rate (BFR) and mineral apposition rate (MAR) in cortical bone in wild type, OPN deficiency induced PTH activation of periosteal BFR and MAR. In cancellous bone, OPN deficiency further enhanced PTH increase in BFR and MAR. Analysis on the cellular bases for these phenomena indicated that OPN deficiency augmented PTH enhancement in the increase in mineralized nodule formation in vitro. OPN deficiency did not alter the levels of PTH enhancement of the excretion of deoxypyridinoline in urine, the osteoclast number in vivo, and tartrate-resistant acid phosphatase-positive cell development in vitro. These observations indicated that OPN deficiency specifically induces PTH activation of periosteal bone formation in the cortical bone envelope.
Spectroscopic Implications for Magnetic Interactions in Metal Complexes with Nitroxide Radicals
Authors: Kaizaki Sumio
Published: April 2003

The influence of the magnetic interaction between a paramagnetic metal ion and a radical ligand upon the spectroscopic (UV-vis and/or NMR) properties will be described and discussed mainly for the mixed ligand complexes, M(L)(X) (M = Ni(II), Cr(III); L = nitroxide radicals such as NIT2py (2-(2-pyridyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazolyl-3-oxide-1-oxyl) or IM2py (2-(2-(pyridyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-1-oxy), X = β-diketonates). For the Ni(II) and Cr(III) complexes, the spin-forbidden d–d bands demonstrated some intensity enhancement and the charge transfer band from the d orbital to the SOMO π* newly appeared in the visible region. Their variable temperature UV-vis spectra substantiated the antiferromagnetic and ferromagnetic interactions as revealed by the magnetic susceptibility measurements. The spectroscopic behaviors with variation of the β-diketonates is examined in connection with magnetic interaction constant J values, exhibiting the coligand effect, e.g., in terms of the exchange mechanism. For the Mn(II), Co(II), Ni(II), and Ln(III) complexes with the NIT2py and/or IM2py or their derivatives and for the Cr(III) and diamagnetic Co(III) complexes with monodentate NIT3- or 4py and IM3- or 4py, the spectroscopic properties are also found to be influenced to the d orbitals from the coordinated nitroxides.
Copper(I) Ion Mediated Self-Assembly of Triple-Stranded Helicates from Oligo(2-ethynylpyridines): Synthesis, Structure, and Properties
Authors: Kawano Tomikazu , Kato Takahiro , Du Chong-Xu , Ueda Ikuo
Published: April 2003

The reaction of oligo(2-ethynylpyridines) (L1–L8) with copper(I) ions proceeded smoothly to afford tri-, tetra-, and pentanuclear triple-stranded helicates (CL1–CL8) in good yields. If a chiral ligand was used, the stereoselective self-assembly of chiral helicates with one particular chirality was achieved in the solid state. Racemization of copper(I) helicates was also observed in solution.
Does the Hydroperoxo Species of Cytochrome P450 Participate in Olefin Epoxidation with the Main Oxidant, Compound I? Criticism from Density Functional Theory Calculations
Authors: Kamachi Takashi , Shiota Yoshihito , Ohta Takehiro , Yoshizawa Kazunari
Published: April 2003

Ethylene epoxidation by an iron(III)-hydroperoxo model of cytochrome P450 Fe(OOH)(C20N4H12)(SCH3) is investigated with the B3LYP density functional theory (DFT) method to look at whether or not the iron(III)–hydroperoxo species can participate in olefin epoxidation with the iron(IV)–oxo species (compound I). The answer is negative. There are two possible entrance channels in the epoxidation reaction, a proximal oxygen transfer mechanism and a distal oxygen transfer mechanism, both mechanisms being stepwise processes involving radical intermediates. In the proximal oxygen transfer mechanism, the homolytic cleavage of the Fe–O bond of the iron(III)–hydroperoxo species initially occurs with a change in the Fe atomic charge from +3 to +2. The proximal oxygen transfer mechanism involves an energetically less stable radical •CH2CH2(OOH). In contrast, in the initial stages of the distal oxygen transfer mechanism, the O–O bond of the hydroperoxo ligand is homolytically cleaved, and the iron(IV)–oxo complex thus formed retains a weak interaction with the hydroxy group of the resultant radical intermediate involving •CH2CH2(OH). This mechanism is more realistic, but the activation energy of the transition state of the O–O bond cleavage is comparable to that of the corresponding transition state by hydrogen peroxide. The present result suggests that the mechanism and energetics of ethylene epoxidation remain unchanged by the involvement of the iron–porphyrin complex. The epoxidation of ethylene by a compound I model is also calculated to increase our understanding of olefin epoxidation by P450. The mechanism and energetics of olefin epoxidation by iron(III)–hydroperoxo species are less plausible than epoxidation by compound I.
Decision Bias in the Newsvendor Problem with a Known Demand Distribution: Experimental Evidence
Authors: Schweitzer Maurice E. , Cachon Gérard P.
Published: April 2003

In the newsvendor problem a decision maker orders inventory before a one period selling season with stochastic demand. If too much is ordered, stock is left over at the end of the period, whereas if too little is ordered, sales are lost. The expected profit-maximizing order quantity is well known, but little is known about how managers actually make these decisions. We describe two experiments that investigate newsvendor decisions across different profit conditions. Results from these studies demonstrate that choices systematically deviate from those that maximize expected profit. Subjects order too few of high-profit products and too many of low-profit products. These results are not consistent with risk-aversion, risk-seeking preferences, Prospect Theory preferences, waste aversion, stockout aversion, or the consequences of underestimating opportunity costs. Two explanations are consistent with the data. One, subjects behave as if their utility function incorporates a preference to reduce ex-post inventory error, the absolute difference between the chosen quantity and realized demand. Two, subjects suffer from the anchoring and insufficient adjustment bias. Feedback and training did not mitigate inventory order errors. We suggest techniques to improve decision making.
Synchronous Unpaced Flow Lines with Worker Differences and Overtime Cost
Authors: Doerr Kenneth H. , Klastorin Theodore D. , Magazine Michael J.
Published: April 2003

In this paper, we consider the design of a synchronous, unpaced flow line where workers operate at different skill levels and overtime is used, if necessary, to meet a daily production quota. The line is unpaced in the sense that items only move to the next workstation when all workers on the line have completed their respective tasks. The design problem in this case is to assign both workers and tasks to workstations to minimize the expected sum of regular and overtime costs. To solve this problem, we develop an optimization algorithm for smaller problems and a heuristic algorithm for larger problems, which we use to investigate the sensitivity of total expected cost to changes in the price of overtime, hiring practices, worker differences, and the overall amount of work time variability. Based on an extensive computational analysis, we found that (1) planned overtime is frequently beneficial, (2) more workers should be hired as worker variability increases, and (3) increases in overtime costs frequently yield a relatively lower percentage increase in total expected cost. Other managerial implications are discussed in the paper.
Measuring the Robustness of Empirical Efficiency Valuations
Authors: Kuntz Ludwig , Scholtes Stefan
Published: April 2003

We study the robustness of empirical efficiency valuations of production processes in an extended Farrell model. Based on input and output data, an empirical efficiency status—efficient or inefficient—is assigned to each of the processes. This status may change if the data of the observed processes change. As illustrated by a capacity planning problem for hospitals in Germany, the need arises to gauge the robustness of empirical efficiency valuations. The example suggests to gauge the robustness of the efficiency valuation for a process with respect to perturbations of prespecified elements of the data. A natural measure of robustness is the minimal perturbation, in terms of a suitable distance function, of the chosen data elements that is necessary to change the efficiency status of the process under investigation. Farrell's (1957) efficiency score is an example of such a robustness measure. We give further examples of relevant data perturbations for which the robustness measure can be computed efficiently. We then focus on weighted maximum norm distance functions, such as the maximal absolute or percentage deviation, but allow for independent perturbations of the elements of an arbitrary a priori fixed subset of the data. In this setting, the robustness measure is naturally related to a certain threshold value for a linear monotone one-parameter family of perturbations and can be calculated by means of a linear programming–based bisection method. Closed form solutions in terms of Farrell's efficiency score are obtained for specific perturbations. Following the theoretical developments, we revisit the hospital capacity planning problem to illustrate the managerial relevance of our techniques.
Solving a System of Linear Diophantine Equations with Lower and Upper Bounds on the Variables
Authors: Aardal Karen , Hurkens Cor A. J. , Lenstra Arjen K.
Published: April 2003

We develop an algorithm for solving a system of diophantine equations with lower and upper bounds on the variables. The algorithm is based on lattice basis reduction. It first finds a short vector satisfying the system of diophantine equations, and a set of vectors belonging to the nullspace of the constraint matrix. Due to basis reduction, all these vectors are relatively short. The next step is to branch on linear combinations of the null-space vectors, which either yields a vector that satisfies the bound constraints or provides a proof that no such vector exists. The research was motivated by the need for solving constrained diophantine equations as subproblems when designing integrated circuits for video signal processing. Our algorithm is tested with good results on real-life data, and on instances from the literature.
A Subsidy-Surplus Model and the Skorokhod Problem in an Orthant
Authors: Ramasubramanian S.
Published: April 2003

We consider the deterministic Skorokhod problem in an orthant of the form [Formula: see text] with (Yw)i(·) nondecreasing, and (Yw)i(·) not increasing while (Zw)i(·) > 0. This can be viewed as a subsidy-surplus model in an interdependent economy. Existence of a unique solution is established under fairly general conditions (viz. with R(·, ·, ·) satisfying a uniform spectral radius condition). Comparison result for (SP) vis-a-vis the usual partial order on the orthant is studied; we show that the more “inward looking” the reflection vectors and the drift, the larger the values of Yw will be but the values of Zw will be smaller. In addition to showing that the Leontief-type output is a feasible subsidy, connection between (SP) and “minimality” of feasible subsidies is discussed (consequently it is suggested that (SP) may be taken as a continuous time feedback-form analogue of open Leontief model).

In the stochastic case, (Y(t), Z(t)) turns out to be a strong Markov process if w(·) arises from aLevy process. Relevance of the comparison result to recurrence/positive recurrence of Z(·) process is pointed out.
Nonhomogeneous Markov Decision Processes with Borel State Space—The Average Criterion with Nonuniformly Bounded Rewards
Authors: Guo Xianping , Liu Jianyong , Liu Ke
Published: April 2003

This paper deals with nonhomogeneous Markov decision processes with Borel state space and nonuniformly bounded rewards under the average criterion. First, under the minorant-type assumption we prove the existence of an appropriate solution to the optimality equations. Second, from the optimality equations we also establish the existence of ε(≥0)-optimal Markov policies under the additional conditions. Third, some sufficient conditions for the validity of the assumptions in this paper and several examples such as inventory/production systems are provided. Finally, as an application of the optimality equations, a rolling horizon algorithm is given.
Decision Making Under Uncertainty: Is Sensitivity Analysis of Any Use?
Authors: Wallace Stein W.
Published: April 2003

Sensitivity analysis, combined with parametric optimization, is often presented as a way of checking if the solution of a deterministic linear program is reliable—even if some of the parameters are not fully known but are instead replaced by a best guess, often a sample mean. It is customary to claim that if the region over which a certain basis is optimal is large, one is fairly safe by using the solution of the linear program. If not, the parametric analysis will provide us with alternative solutions that can be tested. This way, sensitivity analysis is used to facilitate decision making under uncertainty by means of a deterministic tool, namely parametric linear programming. We show in this note that this basic idea of stability has little do with optimality of an optimization problem where the parameters are uncertain.