Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone mouse lung tumorigenesis by arylalkynes, mechanism-based inactivators of cytochrome P450

Arylalkynes such as 4-phenyl-1-butyne (PBY), 5-phenyl-1-pentyne (PPY) and 2-ethynylnaphthalene (2-EN) are suicide inhibitors of cytochrome P450 enzymes. Arylalkyl isothiocyanates such as 6-phenylhexyl isothiocyanate (PHITC) are structurally related to arylalkynes and are known to inhibit the cytochrome P450 mediated metabolic activation and tumorigenicity of a tobacco-specific lung carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In this study, we compared the ability of PBY, PPY, 2-EN and PHITC to inhibit A/J mouse lung tumorigenesis by NNK. Groups of 20 female mice were gavaged with 5 mumol of arylalkyne or PHITC in corn oil. Two hours later they were given a single i.p. injection of 10 mumol NNK. The mice were killed 16 weeks later. PPY and PHITC were both potent inhibitors of tumorigenesis by NNK, reducing lung tumor multiplicity from 8.35 tumors per mouse to 0.40 and 0.35 respectively. PBY and 2-EN also significantly inhibited tumor multiplicity. The results of this study demonstrate that arylalkynes and PHITC are potent inhibitors of NNK induced lung tumorigenesis in A/J mice, consistent with the hypothesis that inhibition of specific cytochrome P450 enzymes is involved in inhibition of tumorigenesis.     

Hepatitis C virus RNA in serum of blood donors with or without elevated transaminase levels

The pattern of hepatitis C virus (HCV) viremia in blood donors who are positive for antibody to HCV (anti-HCV) according to the level of transaminase activity is unclear. A polymerase chain reaction-based HCV RNA detection method was used to study two clearly defined groups of anti-HCV-positive blood donors with repeatedly normal (n = 27) and elevated (n = 17) alanine aminotransferase (ALT) levels. HCV RNA was detected in only 4 of 27 blood donors with normal ALT values and 15 of 17 with elevated ALT values. These results indicate that anti-HCV-positive blood donors with normal ALT levels constitute a heterogeneous group, as HCV viremia is detectable in only a small proportion of cases. Polymerase chain reaction should be useful in the surveillance of anti-HCV-positive blood donors with normal ALT levels, by identifying those who might benefit from further investigation and treatment.     

Uronic acid-containing glycosaminoglycans and keratan sulfate are present in the tectorial membrane of the inner ear: functional implications

The use of growth hormone (GH) as an anabolic agent is limited by its tendency to cause hyperglycemia and by its inability to reverse nitrogen wasting in some catabolic conditions. In a previous study comparing the anabolic actions of GH and IGF-I (insulin-like growth factor I), we observed that intravenous infusions of IGF-I (12 micrograms/kg ideal body wt [IBW]/h) attenuated nitrogen wasting to a degree comparable to GH given subcutaneously at a standard dose of 0.05 mg/kg IBW per d. IGF-I, however, had a tendency to cause hypoglycemia. In the present study, we treated seven calorically restricted (20 kcal/kg IBW per d) normal volunteers with a combination of GH and IGF-I (using the same doses as in the previous study) and compared its effects on anabolism and carbohydrate metabolism to treatment with IGF-I alone. The GH/IGF-I combination caused significantly greater nitrogen retention (262 +/- 43 mmol/d, mean +/- SD) compared to IGF-I alone (108 +/- 29 mmol/d; P < 0.001). GH/IGF-I treatment resulted in substantial urinary potassium conservation (34 +/- 3 mmol/d, mean +/- SE; P < 0.001), suggesting that most protein accretion occurred in muscle and connective tissue. GH attenuated the hypoglycemia induced by IGF-I as indicated by fewer hypoglycemic episodes and higher capillary blood glucose concentrations on GH/IGF-I (4.3 +/- 1.0 mmol/liter, mean +/- SD) compared to IGF-I alone (3.8 +/- 0.8 mmol/liter; P < 0.001). IGF-I caused a marked decline in C-peptide (1,165 +/- 341 pmol/liter; mean +/- SD) compared to the GH/IGF-I combination (2,280 +/- 612 pmol/liter; P < 0.001), suggesting maintenance of normal carbohydrate metabolism with the latter regimen. GH/IGF-I produced higher serum IGF-I concentrations (1,854 +/- 708 micrograms/liter; mean +/- SD) compared to IGF-I only treatment (1,092 +/- 503 micrograms/liter; P < 0.001). This observation was associated with increased concentrations of IGF binding protein 3 and acid-labile subunit on GH/IGF-I treatment and decreased concentrations on IGF-I alone. These results suggest that the combination of GH and IGF-I treatment is substantially more anabolic than either IGF-I or GH alone. GH/IGF-I treatment also attenuates the hypoglycemia caused by IGF-I alone. GH/IGF-I treatment could have important applications in diseases associated with catabolism.     

Effect of guanine nucleotides and temperature on calcitonin gene-related peptide receptor binding sites in brain and peripheral tissues

Recent data have suggested the existence of at least two major classes of calcitonin gene-related peptide (CGRP) receptors in brain and peripheral tissues [Henke et al., Brain Res., 410 (1987) 404-408; Dennis et al., J. Pharmacol. Exp. Ther., 251 (1989) 718-725; ibid, 254 (1990) 123-128; Quirion et al., Ann. NY Acad. Sci., 657 (1992) 88-105]. However, little is currently known in the structure characteristics of CGRP receptors as cloning as yet to be reported. In the present study, the sensitivity of [125I]humanCGRP alpha binding to guanine nucleotides and temperature was investigated in guinea pig atria (prototypical CGRP1 tissue) guinea pig vas deferens (prototypical CGRP2 tissue) and in the rat brain and cerebellum (mixed assay). Binding isotherms of [125I]hCGRP alpha in those four tissue preparations were curvilinear and best fitted to a two-site model under most assay conditions. The high affinity binding component was highly temperature-sensitive and accounted, under experimental conditions, for up to 18% of the total population of receptors. Moreover, these high affinity sites were also highly sensitive to guanine nucleotides (Gpp(NH)p, 100 microM) in all preparations although to a different extend depending upon assay temperatures. Taken together, this suggests that the different CGRP receptor subtypes present in these tissue all belong to a G-protein coupled receptor family.     

Control-canonical-form method applied to generating systems to improve dynamic stability characteristics

Contents The control-canonical-form (CCF) method is introduced for the purpose of applying it to high-order state-space single-input single or multiple-output (SISO or SIMO) and multiple-input multiple-output (MIMO) linear time-invariant system models to determine closed-loop systems (i.e. design robust controllers) from which enchanced dynamic stability characteristics and overall performance of these systems is achieved. The method has been applied successfully to a SISO 6th-order linearized state-space open-loop model (representing a simplified hydro power system), and to a MIMO 8th-order linearized state-space open-loop model (representing an 87.5 kVA synchronous machine with conventional exciter supplying power to an electric utility system through an interconnection network)

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Anwendung der kanonischen Form der Zustandsrückführung auf Erzeugersysteme zur Verbesserung der dynamischen Stabilitätseigenschaften

Übersicht Die Methode der kanonischen Form wird auf lineare zeitinvariante Systeme höherer Ordnung im Zustandsraum angewendet, die eine oder mehrere Eingangsgrößen bei einer oder mehreren Ausgangsgrößen aufweisen. Damit werden robuste Regler entworfen, welche die dynamische Stabilität und das gesamte Betriebsverhalten verbessern. Die Methode wurde erfolgreich auf ein linearisiertes Modell sechster Ordnung mit einem Eingang und einem Ausgang angewendet, das vereinfachend eine Wasserkraftanlage darstellt; außerdem auf ein linearisiertes Zustandsmodell achter Ordnung einer Synchronmaschine 87,5kVA mit konventioneller Erregung, die über ein Verbindungsnetzwerk in das öffentliche Netz einspeist.

     

Integrating intelligent systems into a cooperating community for electricity distribution management

Systems in which semi-autonomous problem-solving agents communicate and cooperate with one another represent an exciting vision of future computing environments. However, if this vision is ever going to result in commercially viable systems, then consideration must be given to the large software base that exists within many organisations. Success requires the ability to incorporate pre-existing systems alongside purpose-built agents in a cooperating community. This requirement is vital because the former represent a substantial resource investment that companies cannot afford to consign to the scrap heap. We report on our experiences of constructing cooperating communities that contain elements that were pre-existing and some that were developed specifically for incorporation into an integrated environment. The general purpose framework of ARCHON (ARchitecture for Cooperative Heterogeneous ON-line systems) provides the underlying technology to facilitate cooperative problem solving, and the exemplar domain is the real world problem of electricity distribution management. The actual application being developed is called CIDIM (Cooperating Intelligent systems for DIstribution system Management). An evolving methodology for designing and developing a mixed system such as this is outlined, based on our experiences in CIDIM and several other real-world industrial applications. It specifies a hybrid top-down and bottom-up approach to integration, identifies the important characteristics that shape multi-agent problem analysis, and outlines key factors that impinge upon the design of the community. this methodology is then used to motivate the design decisions for the CIDIM application. Finally the process of instantiating the individual agents is discussed, some helpful guidelines on testing and evaluating future applications are given, and the implementation of one of CIDIM's cooperative scenarios is described in depth.     

"Adolescent psychopathology: I. Prevalence and incidence of depression and other DSM-III—R disorders in high school students": Correction.

Reports an error in the original article by P. M. Lewinsohn et al ( Journal of Abnormal Psychology, 1993[Feb], Vol 102[1], 133–244). On page 140, in the Total Incidence columns in Table 4, the data for the Attention Deficit row should be switched with that for the Conduct row. (The following abstract of this article originally appeared in record 1993-25780-001.) Data were collected on the point and lifetime prevalences, 1-yr incidence, and comorbidity of depression with other Diagnostic and Statistical Manual of Mental Disorders-III-Revised (DSM-III-R) disorders in a randomly selected sample (n?=?1,710) of high school students at point of entry and at 1-yr follow-up (n?=?1,508). The Schedule for Affective Disorders and Schizophrenia for School-Age Children was used to collect diagnostic information; 9.6% met criteria for a current disorder, more than 33% had experienced a disorder over their lifetimes, and 31.7% of the latter had experienced a 2nd disorder. High relapse rates were found for all disorders, especially for unipolar depression (18.4%) and substance use (15.0%). Female Ss had significantly higher rates at all age levels for unipolar depression, anxiety disorders, eating disorders, and adjustment disorders; male Ss had higher rates of disruptive behavior disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of gait between young adults fitted with the space foot and nondisabled persons

Prosthetic feet having new keel configurations were specially designed to store deformation energy during early and midstance and release it at push-off. These prosthetic components display longitudinal symmetry favoring good energy storage/release capability in the sagittal plane. The need for inverters/everters either as independent components or within the foot structure has long been recognized. This article documents the walking and slow jogging performances of six young adults wearing below-knee prostheses fitted with the Space Foot, a flexible foot prosthesis that provides medio-lateral control at heel-strike and lateral and forward propulsion at push-off. Results indicate that the Space Foot behaves as a flexible keel foot prosthesis. Its gait performances are also good for fast walking; however, the Space Foot's actual design should be modified if used in sporting activities involving running.