Autonomic function in a cohort of children with diabetes

129 diabetic children in Avon County participated in a longitudinal study of the evolution of microvascular disease together with 129 age- and sex-matched controls. Diabetic children had mean (+/- SD) age 12.7 (+/- 3.4) years (range: 3.7-16.8), mean (+/- SD) diabetes duration 3.9 (+/- 3.2) years (range: 0.1-13.4) and mean (+/- SD) HbA1 11.1% (+/- 2.2) (range: 6.5-18.2). Cardiovascular autonomic function was studied by four heart rate (HR) tests using a computerized system of HR monitoring. As a group, diabetic children had higher mean HR (p = 0.0004) and reduced max/min HR ratio while standing (p = 0.001), compared with the control children. HR ratio while standing was the only variable related to diabetes duration (r = -0.20, p = 0.018), while no correlation of HR variables with glycaemic control was found. Twenty diabetic children (15.5%) had one abnormal HR test. Ten diabetic children (7.7%) demonstrated abnormality in two or more HR tests. When compared with the other diabetic children in the cohort, these ten children were found to be younger in age (mean age: 9.4 vs 12.0 yr, p = 0.05), but did not otherwise differ in terms of diabetes duration or glycaemic control. No pubertal or sex effect in the development of diabetic autonomic neuropathy was detected. These findings suggest that autonomic function may be impaired early in childhood diabetes, independent of the duration of the disease or the quality of glycaemic control.     

Reduced performance of male and female athletes at 580 m altitude

Patients with craniocervical mandibular (TMD) disorders can present with tinnitus as a primary or secondary complaint. The embryology and functional anatomy of the middle ear, temporomandibular joint, muscles of mastication and associated tendons, ligaments, blood vessels, nerves and lymphatics was found to be helpful in establishing etiologic concepts which relate tinnitus to these temporomandibular disorders. In addition to etiologic concepts, treatment modalities are described. The authors relate their experiences as well as those of others with different patient populations.     

Demonstration of a word design strategy for DNA computing on surfaces

A strategy for DNA computing on surfaces using linked sets of 'DNA words' that are short oligonucleotides (16mers) is proposed. The 16mer words have the format 5'-FFFFvvvvvvvvFFFF-3' in which 4-8 bits of data are stored in 8 variable ('v') base locations, and the remaining fixed ('F') base locations are used as a word label. Using a template and map strategy, a set of 108 8mers each of which possesses at least a 4 base mismatch with the complements to all the other members of the set (4bm complements) are identified for use as a variable base sequence set. In addition, sets of 4 and 12 word labels of the form ABCD....DCBA that are respectively 8bm and 6bm complements with each other are identified. The 16mers are chosen to have a G/C content of 50% in order to make the thermodynamic stability of the perfectly matched hybridized DNA duplexes similar; a simple pairwise additive method is used to estimate the perfect match and mismatch hybridization thermodynamics. A series of preliminary experiments are presented that use small arrays of 16mers attached to chemically modified gold surfaces and fluorescently labeled complements to study the hybridization adsorption and enzymatic manipulation of the oligonucleotides.     

Modification of the water oxidizing complex in leaves of the dgd1 mutant of Arabidopsis thaliana deficient in the galactolipid digalactosyldiacylglycerol

The primary biochemical defect in the genetically well characterized dgd1 mutant of Arabidopsis thaliana causes a 90% reduction in the relative amount of the galactolipid digalactosyldiacylglycerol (DGDG). To study the effect of this DGDG deficiency on photosystem II (PS II), time-resolved transients of laser-flash-induced changes of the relative fluorescence quantum yield Fvar,rel(t) were measured in whole leaves from wild-type and the dgd1 mutant. The results obtained reveal (i) in untreated leaves the decay kinetics of Fvar, rel(t) reflecting QA.- reoxidation by endogenous plastoquinone are very similar in wild-type and the dgd1 mutant at room temperature, (ii) the Arrhenius plot of the temperature dependence of electron transfer from QA.- to QB exhibits a break point at about 19 degrees C in wild-type and about 12 degrees C in the dgd1 mutant, (iii) in leaves treated with DCMU the slow reoxidation of QA.- by the PS II donor side is blocked to a much higher extent in the dgd1 mutant (about 50%) compared to wild-type (about 10%), and iv) the normalized amplitude of Fvar,rel(t = 1 micros) reflecting the percentage of fast P680.+ reduction by YZ exhibits a characteristic period four oscillation in wild-type while this feature is strongly damped in the dgd1 mutant. Presumably, the severe DGDG deficiency is causing the thermal down shift of a lipid phase transition that affects the QA.- reoxidation by QB. Most strikingly, the properties of the WOC are modified as a result of reduced DGDG content. Thus, the lipid DGDG appears to be of structural relevance for the WOC.     

Structure-activity relationship study of 16 a-thiocamptothecins: an integrated in vitro and in silico approach

The instability of the hydroxylactone E ring represents a critical drawback of camptothecins, because the lactone ring is recognized to be essential for stabilization of topoisomerase I‐mediated DNA cleavage. In an attempt to investigate the effect of the thiopyridone pharmacophofore on the molecular and pharmacological features of the drug, we prepared a series of novel 16 a‐thiocamptothecin analogues. Due to the sulfur atom, a destabilization of the hydrogen bond between the hydroxy group in position 17 of the opened E ring and the carbonyl of the pyridone moiety is predicted, thus shifting the equilibrium toward the closed lactone form and increasing the lipophilic properties of the compounds. This feature was associated with superior antiproliferative potency, with reduced interaction with the human serum albumin and with substantial increase of the persistence of the topoisomerase I–DNA cleavable complex. These effects were prominent for thio‐SN38, the most active compound of the series. The favorable interactions at the molecular and cellular level of the reported thiocamptothecins confer promising features, and these compounds warrant preclinical development.     

Sweet-tasting protein monellin is related to the cystatin family of thiol proteinase inhibitors

The structure of the intensely sweet protein monellin, isolated from an African berry, and the structures of two thiol proteinase inhibitors, cystatin and stefin B, are found to be very similar. An alignment of sequences of monellin and the inhibitors, deduced from the structural comparisons, has been extended to include other members of the cystatin superfamily. There is a significant homology (up to 23% identical residues) with oryzacystatins, the only well defined plant cystatins. These results clearly indicate that monellin is a close relative of cystatins. Monellin and cystatins do not have the same sequence in the regions homologous to the cystatin active site. It is suggested here, however, that this region in monellin may be essential for a function in situ, because one of the loops comprising this part of the structure is found to be cleaved.     

The contribution of attention to the right visual field advantage for word recognition

Perceptual asymmetries have been explained by structural, attentional bias and attentional advantage models. Structural models focus on asymmetries in the physical access information has to the hemispheres, whereas attentional models focus on asymmetries in the operation of attentional processes. A series of experiments was conducted to assess the contribution of attentional mechanisms to the right visual field (RVF) advantage found for word recognition. Valid, invalid and neutral peripheral cues were presented at a variety of stimulus onset asynchronies to manipulate spatial attention. Results indicated a significant RVF advantage and cueing effect. The effect of the cue was stronger for the left visual field than the RVF. This interaction supports the attentional advantage model which suggests that the left hemisphere requires less attention to process words. The attentional asymmetry is interpreted in terms of the different word processing styles used by the left and right hemispheres. These results have ramifications for the methodology used in divided visual field research and the interpretation of this research.     

Adrenocortical SPECT using iodine-131 NP-59

Adrenal scintigraphy with 131I-labeled 6-beta-iodomethyl-19-norcholesterol (NP-59) is a technically demanding and complex procedure. However, it can provide crucial and unique information about the functional status of the adrenal glands and guide the appropriate therapeutic management of patients with biochemically proven disease. Since the introduction of this new investigational drug, scintigraphic imaging has been performed using conventional planar techniques. We present an interesting case of primary aldosteronism in which planar scintigraphy and SPECT were combined in an attempt to increase the sensitivity of the study. SPECT revealed scintigraphic evidence of bilateral adrenocortical hyperplasia. Interestingly, the CT scan of this patient showed only an equivocal abnormality in the left adrenal gland, suggestive of an adenoma.