DETERMINATION OF GUSTATORY SUCROSE THRESHOLD IN WATER BY USE OF A LINEAR SUCROSE GRADIENT

A novel experimental method was developed which allows the determination of the threshold concentration of sucrose by use of a linear sucrose gradient in water. With this method a continuous tasting of the test-liquid is possible. A panel of 15 persons experienced in taste-testing was used. Three gradients of different steepness were applied: 0 to 1.5% (w/w) sucrose in 2 min (I), 3 min (II) and 4 min (III). The results of the new method were compared with those of the standard method (DIN). With gradients I and II we found values which were significantly higher than those of the standard method (I: 0.49% (w/w); II: 0.46% (w/w); DIN: 0.31% (w/w)), whereas with gradient III the same threshold value was found as with the DIN-Method (III: 0.32% (w/w)).     

Effect of neurotensin on pancreatic function in man

The effect of neurotensin on submaximally-stimulated hepatobiliary and pancreatic secretion was studied in 6 healthy subjects. An intravenous infusion of neurotensin 1.4 ± 0.3 pmol/kg/min, designed to reproduce plasma neurotensin immunoreactivity levels within the physiological range, produced a significant increase in pancreatic bicarbonate output. Plasma concentrations of pancreatic polypeptide rose by 83 ± 16 pmol/l and were associated with a small reduction in trypsin, but no significant change in bilirubin outputs.     

Delimitation of the maritime boundary in the gulf of Maine area

The compulsory dispute settlement regime included in the 1982 Law of the Sea Convention is recognized as one of the most comprehensive in a modern international convention. Yet, in the recent application of this regime, the question has arisen as to whether the procedural prerequisites associated with the LOS Convention's compulsory dispute settlement mechanism are so arduous as to avoid binding and compulsory jurisdiction in most instances. This article addresses that question by examining, in particular, the reasoning of the Southern Bluefin Tuna arbitration tribunal, which found Article 281 of Section 1 of the LOS Convention to bar jurisdiction to the compulsory dispute settlement mechanism prescribed by the Convention, and offers suggestions as to how states might distinguish or overcome the barriers imposed by the Southern Bluefin Tuna tribunal in future cases.     

The role of human rhinovirus in immunology, COPD, and corresponding treatments

The common cold is most often a result of human rhinovirus (HRV) infection. Common cold symptoms including rhinorrhea and nasal obstruction frequently occur during HRV infection of the upper respiratory tract. Conversely, HRV may also infect the epithelial cells of the lower respiratory tract. Symptom severity associated with HRV infection ranges from mild to potentially serious depending on a person’s susceptibility and pre-existing condition, such as chronic obstructive pulmonary disease. An over active host immune response is believed to be the primary contributor to HRV pathogenesis. Enhanced activity of various host cell cytokines and granulocytes mediate specific cellular pathways inducing many of the symptoms associated with HRV infection. There are over 100 serotypes of HRV which can be further categorized based on the specific characteristics of each type. The two main categories of HRV consist of the major and minor groups. The unique host cell receptor is the distinguishing factor between these two groups. Yet, these viruses may also differ in mechanism of infection and replication. Due to the high frequency of hospital and clinical visits and the corresponding economic burden, novel therapies are of interest. Several different treatment options varying from herbal remedies to anti-viral drugs have been studied. However, the vast number of HRV serotypes complicates the progress of developing a universal treatment for attenuating HRV infection.     

Exaggerated effect of fluvoxamine in heterozygote serotonin transporter knockout mice

Clearance rates for serotonin (5-HT) in heterozygote (+/-) and homozygote (-/-) serotonin transporter (5-HTT) knockout (KO) mice have not been determined in vivo. Moreover, the effect of selective serotonin reuptake inhibitors (SSRIs) on 5-HT clearance in these mice has not been examined. In this study, the rate of clearance of exogenously applied 5-HT was measured in the CA3 region of the hippocampus of anesthetized mice using high-speed chronoamperometry. Compared with wild-type mice, the maximal rate of 5-HT clearance from extracellular fluid (ECF) was decreased in heterozygotes and more markedly so in KO mice. Heterozygote mice were more sensitive to the 5-HT uptake inhibitor, fluvoxamine, resulting in longer clearance times for 5-HT than in wild-type mice; as expected, the KO mice were completely unresponsive to fluvoxamine. There were no associated changes in norepinephrine transporter density, nor was there an effect of the norepinephrine uptake inhibitor, desipramine, on 5-HT clearance in any genotype. Thus, adaptive changes in the norepinephrine transport system do not occur in the CA3 region of hippocampus as a consequence of 5-HTT KO. These data highlight the potential of the heterozygote 5-HTT mutant mice to model the dynamic in vivo consequences of the human 5-HTT polymorphism.     

Cardiac troponin T isoforms affect the Ca2+ sensitivity and inhibition of force development. Insights into the role of troponin T isoforms in the heart

At least four isoforms of troponin T (TnT) exist in the human heart, and they are expressed in a developmentally regulated manner. To determine whether the different N-terminal isoforms are functionally distinct with respect to structure, Ca(2+) sensitivity, and inhibition of force development, the four known human cardiac troponin T isoforms, TnT1 (all exons present), TnT2 (missing exon 4), TnT3 (missing exon 5), and TnT4 (missing exons 4 and 5), were expressed, purified, and utilized in skinned fiber studies and in reconstituted actomyosin ATPase assays. TnT3, the adult isoform, had a slightly higher alpha-helical content than the other three isoforms. The variable region in the N terminus of cardiac TnT was found to contribute to the determination of the Ca(2+) sensitivity of force development in a charge-dependent manner; the greater the charge the higher the Ca(2+) sensitivity, and this was primarily because of exon 5. These studies also demonstrated that removal of either exon 4 or exon 5 from TnT increased the cooperativity of the pCa force relationship. Troponin complexes reconstituted with the four TnT isoforms all yielded the same maximal actin-tropomyosin-activated myosin ATPase activity. However, troponin complexes containing either TnT1 or TnT2 (both containing exon 5) had a reduced ability to inhibit this ATPase activity when compared with wild type troponin (which contains TnT3). Interestingly, fibers containing these isoforms also showed less relaxation suggesting that exon 5 of cardiac TnT affects the ability of Tn to inhibit force development and ATPase activity. These results suggest that the different N-terminal TnT isoforms would produce different functional properties in the heart that would directly affect myocardial contraction.     

Myosin essential light chain in health and disease

The essential light chain of myosin (ELC) is known to be important for structural stability of the alpha-helical lever arm domain of the myosin head, but its function in striated muscle contraction is poorly understood. Two ELC isoforms are expressed in fast skeletal muscle, a long isoform and its NH(2)-terminal approximately 40 amino acid shorter counterpart, whereas only the long ELC is observed in the heart. Biochemical and structural studies revealed that the NH(2)-terminus of the long ELC can make direct contacts with actin, but the effects of the ELC on the affinity of myosin for actin, ATPase, force, and the kinetics of force generating myosin cross-bridges are inconclusive. Myosin containing the long ELC has been shown to have slower cross-bridge kinetics than myosin with the short isoform. A difference was also reported among myosins with long isoforms. Increased shortening velocity was observed in atrial compared with ventricular muscle fibers. The common findings suggest that ELC provides the fine tuning of the myosin motor function, which is regulated in an isoform and tissue-dependent manner. The functional importance of the ELC is further implicated by the discovery of ELC mutations associated with Familial Hypertrophic Cardiomyopathy. The pathological phenotypes vary in severity, but more notably, almost all ELC mutations result in sudden cardiac death at a young age. This review summarizes the functional roles of striated muscle ELC in normal healthy muscle and in disease. Transgenic animal models and phenotypic characterization of ELC-mediated remodeling of the heart are also discussed.     

Energy expenditure and influence of physiologic factors during marathon running

This study examined energy expenditure and physiologic determinants for marathon performance in recreational runners. Twenty recreational marathon runners participated (10 males aged 41 +/- 11.3 years, 10 females aged 42.7 +/- 11.7 years). Each subject completed a V(.-)O2max and a 1-hour treadmill run at recent marathon pace, and body composition was indirectly determined via dual energy X-ray absorptiometry. The male runners exhibited higher V(.-)O2max (ml x kg(-1) x min(-1)) values (52.6 +/- 5.5) than their female counterparts (41.9 +/- 6.6), although ventilatory threshold (T-vent) values were similar between groups (males: 76.2 +/- 6.1 % of V(.-)O2max, females: 75.1 +/- 5.1%). The male runners expended more energy (2,792 +/- 235 kcal) for their most recent marathon as calculated from the 1-hour treadmill run at marathon pace than the female runners (2,436 +/- 297 kcal). Body composition parameters correlated moderately to highly (r ranging from 0.50 to 0.87) with marathon run time. Also, V(.-)O2max (r = -0.73) and ventilatory threshold (r = -0.73) moderately correlated with marathon run time. As a group, the participants ran near their ventilatory threshold for their most recent marathon (r = 0.74). These results indicate the influence of body size on marathon run performance. In general, the larger male and female runners ran slower and expended more kilocalories than smaller runners. Regardless of marathon finishing time, the runners maintained a pace near their T-vent, and as T-vent or V(.-)O2max increased, marathon performance time decreased.     

A new class of glycogen phosphorylase inhibitors

A new class of diacid analogues that binds at the AMP site not only are very potent but have approximately 10-fold selectivity in liver versus muscle glycogen phosphorylase (GP) in the in vitro assay. The synthesis, structure, and in vitro and in vivo biological evaluation of these liver selective glycogen phosphorylase inhibitors are discussed.