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PubMed1996

Development of Alzheimer-related neurofibrillary changes in the neocortex inversely recapitulates cortical myelogenesis.

The pattern of neurofibrillary changes which gradually develops in the course of Alzheimer's disease bears a striking resemblance to the inverse sequence of cortical myelination. Factors released by oligodendrocytes exert a strong influence upon nerve cells and suppress disordered neuritic outgrowth. It is suggested that the lack of such factors due to premature dysfunction of oligodendrocytes leads to alterations of the neuronal cytoskeleton and eventually to the appearance of Alzheimer-type neurofibrillary changes.

Alzheimer Disease↗
PubMed2005

Alternative strategies for exercise critical power estimation in patients with COPD.

Exercise critical power (CP) has been shown to represent the highest sustainable work rate (WR) in patients with chronic obstructive pulmonary disease (COPD). Parameter estimation, however, depends on 4 high-intensity tests performed, on different days, to the limit of tolerance (T(lim)). In order to establish a milder protocol that would be more suitable for disabled patients, we contrasted CP derived from 4, 3 and 2 tests (CP4, CP3 and CP2) in 8 males with moderate COPD. In addition, CP was calculated from 2 single-day tests performed on an inverse sequence (CP(2AB) and CP(2BA)): CP values within 5 W from CP4 were assumed as "clinically-acceptable" estimates. We found that [CP4-CP3] and [CP4-CP2] differences were within 5 W in 8 and 6 patients, respectively (95% confidence interval of the differences = -1.3 to 3.5 W and -11.5 to 6.5 W). There was a systematic decline on T(lim) when an exercise bout was performed after a previous test on the same day (P<0.05). Consequently, substantial differences were found between CP4 and any of the CP estimates obtained from single-day tests. In conclusion, clinically-acceptable estimates of CP can be obtained by using 3 or, in most circumstances, 2 constant WR tests in patients with moderate COPD--provided that they are not performed on the same day.

Aged↗
PubMed1998

Long-chain n-alkanols and arachidonic acid interfere with the Vm-sensitive gating mechanism of gap junction channels.

Experiments were carried out on preformed cell pairs and induced cell pairs of an insect cell line (mosquito Aedes albopictus, clone C6/36). The coupling conductance, gj, was determined with the dual voltage-clamp method. Exposure of preformed cell pairs to lipophilic agents, such as long-chain n-alkanols (n-hexanol, n-heptanol, n-octanol, n-nonanol, n-decanol) or arachidonic acid, provoked a decrease in gj. Hyperpolarization of both cells led to a recovery of gj. Systematic studies revealed that this phenomenon is caused by a shift of the sigmoidal relationship gj(ss) = f(Vm) towards more negative values of Vm (where gj(ss) = conductance at steady-state; Vm = membrane potential). The shift was dose dependent, it developed with time and was reversible. The longer the hydrocarbon chain of n-alkanols, the lower was the concentration required to produce a given shift. Besides shifting the function gj(ss) = f(Vm), arachidonic acid decreased the maximal conductance, gj(max). Single-channel records gained from induced cell pairs revealed that the lipophilic agents interfere with the Vm-sensitive slow channel gating mechanism. Application provoked slow current transitions (transition time: 5-40 ms) between an open state of the channel (i.e. main state or residual state) and the closed state; subsequently, fast channel transitions (transition time: < 2 ms) involving the main state and the residual state ceased completely. Hyperpolarization of Vm or washout of the lipophilic agents gave rise to the inverse sequence of events. The single-channel conductances gammaj(main state) and gammaj(residual state) were not affected by n-heptanol. We conclude that long-chain n-alkanols and arachidonic acid interact with the Vm-sensitive gating mechanism.

1-Octanol↗
PubMed1982

Reversal or prevention of diuretic-induced alterations in serum lipoproteins with betablockers.

In 18 patients with essential hypertension serum low density lipoprotein cholesterol (LDL-C) was significantly (P less than 0.001) increased following short-term chlorthalidone therapy, but not during combination therapy with chlorthalidone and a betablocker. This tendency was similar in two subgroups which were studied with an inverse sequence of drug administration. In Group I (11 men), a 22% increase (P less than 0.01) in LDL-C during chlorthalidone monotherapy was restored to normal 6 weeks after addition to a betablocker to the diuretic; in Group II (5 men, 2 postmenopausal women) LDL-C levels were increased by 41% (P less than 0.05) 6 weeks after withdrawal of the betablocker from the combination therapy. No significant changes occurred during either the treatment phase in high density lipoprotein cholesterol or apoprotein B levels. It is concluded that combination therapy with a betablocker may prevent or reverse an increase in serum LDL-C associated with short-term chlorthalidone monotherapy.

Adolescent↗
PubMed2006

Decrease in blood triglycerides associated with the consumption of eggs of hens fed with food supplemented with fish oil.

BACKGROUND: n-3 polyunsaturated fatty acids (n-3 PUFA) convey several health benefits, including a reduction of serum concentration of triglycerides (TG). AIM: To examine the effect on blood lipids, particularly TG, of a diet with n-3 PUFA enriched eggs in healthy volunteers in the Seychelles (Indian Ocean). METHODS: Double-blind crossover trial with one group of volunteers fed with 5 normal eggs per week during 3 weeks followed by 5 enriched eggs per week during the next 3 weeks while the other group received eggs in the inverse sequence. Hen feed was supplemented at 5% with tuna oil. Enriched eggs contained nine times more n-3 PUFA than usual eggs (mainly docosahexaenoic acid). RESULTS: Twenty-five healthy volunteers participated in the study. Based on pooled results observed during the two 3-week periods, consumption of enriched eggs was associated with a significant 16-18% decrease in serum triglycerides (P<0.01) but with no significant difference in serum LDL-cholesterol and HDL-cholesterol. Serum LDL-cholesterol increased during the first 3-week period and decreased during the second 3-week period with both normal and enriched eggs. Participants did not report a systematic preference for either type of eggs. CONCLUSIONS: Reasonable consumption of n-3 PUFA enriched eggs was associated with a significant decrease in serum triglycerides. These eggs could be a palatably acceptable source of n-3 PUFA.

Adult↗
PubMed1998

Promotion of transition metal-induced reactive oxygen species formation by beta-amyloid.

beta-amyloid protein appears to be involved in the neural degeneration associated with Alzheimer's disease. However, its mechanism of action is poorly understood. The ability of the neurotoxic peptide fragment (25-35) derived from beta-amyloid, to promote the generation of reactive oxygen species (ROS) by a postmitochondrial fraction (P2) derived from rat cerebrocortex, has been examined. The peptide fragment, when incubated together with P2, did not cause excess ROS formation. However, 10 microM FeSO4 or 10 microM CuSO4 were able to enhance ROS production in the P2 fraction and this was increased further in the concurrent presence of the 25-35 fragment. The corresponding inverse sequence non-neurotoxic peptide (35-25) had no parallel ability to augment iron-stimulated ROS production suggesting a degree of specificity for the observed effect. There was no formation of excess ROS when the 25-35 peptide and 0.5 mM Al2(SO4)3 were incubated with the P2 fraction. However in the presence of both aluminum and iron salts together with the 25-35 peptide, ROS production was augmented to a level significantly higher than that in the absence of aluminum. Polyglutamate, a peptide reported to mitigate aluminum toxicity had no effect on iron-related ROS generation but completely prevented its further potentiation by aluminum. The results indicate that beta-amyloid is able to potentiate the free-radical promoting capacity of metal ions such as iron, copper and aluminum. Such potentiation may be a relevant mechanism underlying beta-amyloid-induced degeneration of nerve cells.

Alum Compounds↗
PubMed1993

A clomiphene citrate and tamoxifen citrate combination therapy: a novel therapy for ovulation induction.

OBJECTIVE: To assess the efficacy of a clomiphene citrate (CC) and tamoxifen citrate (CC/tamoxifen) combination therapy in ovulation induction by comparing with a CC alone therapy. DESIGN: A randomized cross-over study with CC alone and CC/tamoxifen combination therapies for 20 normoprolactinemic anovulatory women. Randomly selected 10 of the 20 women (group A) underwent a CC alone therapy (100 mg CC during cycle days 5 to 9) for the initial three consecutive treatment cycles and a CC/tamoxifen combination therapy (50 mg CC and 20 mg tamoxifen during cycle days 5 to 9) for the subsequent three consecutive treatment cycles. The remaining 10 (group B) were treated similarly but with the inverse sequence. Ovulation was documented when a high BBT phase persisted for 11 days or more, when midluteal serum P levels exceeded 7 ng/mL (22.3 nmol/L), or when pregnancy ensued. RESULTS: The rates of ovulatory/treated, pregnant/treated, and pregnant/ovulatory cycles were 42 of 56 (75.0%), 3 of 47 (6.4%), and 3 of 35 (8.6%) for CC/tamoxifen, respectively. Those were 25 of 57 (43.9%), 1 of 48 (2.1%), and 1 of 21 (4.8%) for CC, respectively. Clomiphene citrate/tamoxifen was more effective in ovulation induction than CC. All the pregnancies were normal and single. None of the treatments was accompanied by any remarkable side effects. CONCLUSION: Clomiphene citrate/tamoxifen is a novel treatment modality of ovulation induction with high efficacy.

Adult↗
PubMed2003

Catalytic decomposition of hydrogen peroxide and 4-chlorophenol in the presence of modified activated carbons.

The objective of this research was to examine the heterogeneous catalytic decomposition of H(2)O(2) and 4-chlorophenol (4-CP) in the presence of activated carbons modified with chemical pretreatments. The decomposition of H(2)O(2) was suppressed significantly by the change of surface properties including the decreased pH(pzc) modified with oxidizing agent and the reduced active sites occupied by the adsorption of 4-CP. The apparent reaction rate of H(2)O(2) decomposition was dominated by the intrinsic reaction rates on the surface of activated carbon rather than the mass transfer rate of H(2)O(2) to the solid surface. By the detection of chloride ion in suspension, the reduction of 4-CP was not only attributed to the advanced adsorption but also the degradation of 4-CP. The catalytic activity toward 4-CP for the activated carbon followed the inverse sequence of the activity toward H(2)O(2), suggesting that acidic surface functional group could retard the H(2)O(2) loss and reduce the effect of surface scavenging resulting in the increase of the 4-CP degradation efficiency. Few effective radicals were expected to react with 4-CP for the strong effect of surface scavenging, which could explain why the degradation rate of 4-CP observed in this study was so slow and the dechlorination efficiency was independent of the 4-CP concentration in aqueous phase. Results show that the combination of H(2)O(2) and granular activated carbon (GAC) did increase the total removal of 4-CP than that by single GAC adsorption.

Adsorption↗
PubMed2001

Total synthesis of 2',3',4',5',5' '-(2)h(5)-ribonucleosides: the key building blocks for NMR structure elucidation of large RNA.

The diastereospecific chemical syntheses of uridine-2',3',4',5',5' '-(2)H(5) (21a), adenosine-2',3',4',5',5' '-(2)H(5) (21b), cytidine-2',3',4',5',5' '-(2)H(5)(2)H(5) (21c), and guanosine-2',3',4',5',5' '-(2)H(5) (21d) (>97 atom % (2)H at C2', C3', C4', and C5'/C5' ') have been achieved for their use in the solution NMR structure determination of oligo-RNA by the Uppsala "NMR-window" concept (refs 4a-c, 5a, 6), in which a small (1)H segment is NMR-visible, while the rest is made NMR-invisible by incorporation of the deuterated blocks 21a-d. The deuterated ribonucleosides 21a-d have been prepared by the condensation of appropriately protected aglycone with 1-O-acetyl-2,3,5-tri-O-(4-toluoyl)-alpha/beta-D-ribofuranose-2,3,4,5,5'-(2)H(5) (19), which has been obtained via diastereospecific deuterium incorporation at the C2 center of appropriate D-ribose-(2)H(4) derivatives either through an oxidation-reduction-inversion sequence or a one-step deuterium-proton exchange in high overall yield (44% and 24%, respectively).

Deuterium↗
PubMed1999

Preparation of a microcrystalline suspension formulation of Lys(B28)Pro(B29)-human insulin with ultralente properties.

The monomeric analogue, Lys(B28)Pro(B29)-human insulin (LysPro), has been crystallized using similar conditions employed to prepare extended-acting insulin ultralente formulations. In the presence of zinc ions, sodium acetate and sodium chloride, but without phenolic preservative, LysPro surprisingly forms small rhombohedral crystals with similar morphology to human insulin ultralente crystals with a mean particle size of 20 +/- 1 microm. X-ray powder diffraction studies on the LysPro crystals prior to dilution in ultralente vehicle ([NaCl] = 1.2 M) revealed the presence of T(3)R(3)(f) hexamers. Consistent with human insulin ultralente preparations, LysPro crystals formulated as an ultralente suspension ([NaCl] = 0. 12 M) contain T(6) hexamers indicating that a conformational change occurs in the hexamer units of the crystals upon dilution of the salt concentration. The pharmacological properties of subcutaneously administered ultralente LysPro (ULP) were compared to ultralente human insulin (UHI) using a conscious dog model (n = 5) with glucose levels clamped at basal. There were no statistically significant differences between the kinetic and dynamic responses of ULP compared to UHI [C(max) (ng/mL): 3.58 +/- 0.76, ULP and 3.61 +/- 0. 66, UHI; T(max) (min): 226 +/- 30, ULP and 185 +/- 42, UHI; R(max) (mg/kg min): 11.2 +/- 1.9, ULP and 13.3 +/- 2.0, UHI; and T(Rmax) (min): 336 +/- 11, ULP and 285 +/- 57, UHI]. Although the Pro to Lys sequence inversion destabilizes insulin self-assembly and greatly alters the time action of soluble LysPro preparations, this modification has now been found neither to prevent the formation of ultralente crystals in the absence of phenolics nor to compromise the protracted activity of the insulin analogue suspension.

Animals↗
PubMed2005

Reentrant morphological transitions in copolymer micelles with pH-sensitive corona.

In contrast to self-assembled aggregates of conventional ionic (including polymeric) surfactants the equilibrium micelles of diblock copolymer with a pH-sensitive polyelectrolyte block can exhibit two inverse sequences of morphological transitions triggered by an increase in solution salinity. The direct sequence of the sphere-cylinder-lamella transitions is similar to that for the copolymer with a strongly dissociating ionic block and occurs at a high salt concentration in solution. The abnormal reversed sequence of the lamella-cylinder-sphere transitions is predicted to occur at relatively low ionic strength in solution. The origin of the reentrant transitions is coupling between aggregation and ionization in copolymer micelles.

Letter↗
PubMed1981

Beta-receptor-blocking agents may reverse or prevent diuretic-induced increases in serum low-density lipoprotein cholesterol.

1. The effect of treatment with a thiazide-like diuretic alone or combined with a beta-adrenoceptor blocker on serum lipoproteins was investigated in 35 patients with essential hypertension. 2. In group I (18 patients), serum low-density lipoprotein cholesterol was increased (P less than 0.001) during monotherapy with chlorthalidone (100 mg/day) but not during combined chlorthalidone--beta-blocker therapy. 3. This tendency was similar in subgroups studied with an inverse sequence of drug administration. In subgroup IA (11 men), a 22% increase (P less than 0.01) in low-density lipoprotein cholesterol after 6 weeks of chlorthalidone was reversed after use of a beta-blocker as well as chlorthalidone; in subgroup IB (five men, two post-menopausal women), low-density lipoprotein cholesterol was increased by 41% (P less than 0.05) above placebo values 6 weeks after withdrawal of the beta-blocker from combination therapy. 4. In group II (18 men), low-density lipoprotein cholesterol was increased by 13% (P less than 0.025) after 4 weeks of monotherapy with clopamide (5 mg/day) but restored to control levels 4 weeks after addition of pindolol (10 mg/day). 5. No significant changes occurred during any treatment phase in high-density lipoprotein cholesterol. 6. Certain beta-receptor blocking agents may prevent or reverse diuretic-induced increases in serum low-density lipoprotein cholesterol.

Adolescent↗
PubMed2003

Rapid atrial pacing does not decrease the atrial defibrillation threshold.

The aim of the study was to evaluate the effect of preshock atrial pacing on the atrial defibrillation threshold (DFT) during internal cardioversion of AF. The implantable atrial defibrillator has been added to the therapeutic options for patients with recurrent episodes of persistent AF. Although the device is efficient in restoring sinus rhythm, patient discomfort is a limitation. Methods that lower the ADFT are needed. Eleven patients with AF underwent internal cardioversion. In a randomized, crossover design, ADFT testing was performed, applying a step-up protocol starting at 100 V. Rapid atrial pacing was performed with a right atrial catheter for 20 seconds at 90% of the average cycle length of the fibrillatory waves and was immediately followed by a biphasic defibrillation shock. At each energy level, pacing + shock was compared to shock only, until the level at which sinus rhythm was restored by both modes. The step-up protocol was thereafter repeated using the inverse sequence of the two modes. A total of 19 ADFTs were obtained. For 10 the ADFT was lower with pacing + shock, in 4 equal and in 5 higher, than with shock only. The ADFT (mean +/- SD) with pacing + shock was 260 +/- 84 V(3.4 +/- 2.9 J) and did not differ from shock only: 268 +/- 85 V(3.8 +/- 3.0 J) (P > 0.05). The coefficient of variation and the coefficient of reproducibility for pacing + shock was 16% and 60 V, respectively, and for shock only 17% and 61 V. Rapid atrial pacing did not influence the internal ADFT in AF. The randomized, crossover protocol used was reproducible between different modes, and seems useful when testing the impact of different interventions on the ADFT.

Atrial Fibrillation↗
PubMed2001

Magnetic resonance imaging of the wrist.

Optimal magnetic resonance (MR) imaging of the wrist requires a high field strength magnet and a dedicated wrist coil to achieve high-resolution images. Using current MR sequences, detailed images of articular cartilage and the supporting ligaments and tendons can be obtained. Evaluation of the triangular fibrocartilage as well as the extrinsic and intrinsic ligaments of the wrist is possible with thin-slice three-dimensional volumetric gradient recalled sequences. Fast inversion recovery sequences, used to achieve fat suppression in peripheral joints such as the wrist, allow for detection of acute osseous trauma, which is often radiographically occult. Cartilage-sensitive imaging allows for evaluation of conditions in the skeletally immature patient, such as chronic physeal loading in the adolescent gymnast, as well as detection of the sequelae of altered biomechanics in the adult, as in the ulnolunate impaction syndrome. Moreover, contrast-enhanced magnetic resonance angiography permits a relatively noninvasive evaluation of peripheral vascular disease, obviating the need for an intraarticular injection.

Adolescent↗
PubMed1999

The mating-type and pathogenicity locus of the fungus Ustilago hordei spans a 500-kb region.

The fungal pathogen Ustilago hordei causes the covered smut disease of barley and oats. Mating and pathogenicity in this fungus are controlled by the MAT locus, which contains two distinct gene complexes, a and b. In this study, we tagged the a and b regions with the recognition sequence for the restriction enzyme I-SceI and determined that the distance between the complexes is 500 kb in a MAT-1 strain and 430 kb in a MAT-2 strain. Characterization of the organization of the known genes within the a and b gene complexes provided evidence for nonhomology and sequence inversion between MAT-1 and MAT-2. Antibiotic-resistance markers also were used to tag the a gene complex in MAT-1 strains (phleomycin) and the b gene complex in MAT-2 strains (hygromycin). Crosses were performed with these strains and progeny resistant to both antibiotics were recovered at a very low frequency, suggesting that recombination is suppressed within the MAT region. Overall, the chromosome homologues carrying the MAT locus of U. hordei share features with primitive sex chromosomes, with the added twist that the MAT locus also controls pathogenicity.

Avena↗
PubMed2003

Influence of surface modification on catalytic activity of activated carbon toward decomposition of hydrogen peroxide and 2-chlorophenol.

The objective of this research was to investigate the influence of the activated carbons modified by chemical treatment on the surface catalyzed loss of H2O2 and 2-CP. The characteristics of the modified activated carbons were examined by several techniques including nitrogen adsorption, SEM, and EDS. The H2O2 decomposition rate would be suppressed significantly either by the change of surface properties modified with chemical treatment or the reduction of active sites occupied with the adsorption of 2-CP. In addition, the H2O2 decomposition rate with activated carbons within a specific time can be described by a second-order kinetic expression with respect to the concentration of GAC and H2O2 in the absence or presence of 2-CP. The catalytic activities of the three activated carbons toward 2-CP reduction followed the inverse sequence of those toward H2O2 loss, implying that acidic surface functional group could retard the H2O2 loss and reduce the effect of surface scavenging resulting in increasing the reduction efficiency of 2-CP. By the detection of chloride ions in reaction mixture, it can be demonstrated that the reduction of 2-CP was not only attributed to the advanced adsorption but also the oxidation of the 2-CP with effective radicals. The real oxidation efficiency of 2-CP for the activated carbon modified with hot nitric acid was observed between 0.04 and 0.01 (mol/mol), offering a comparable efficiency to that of the other oxidation system using metal oxide as catalyst.

Adsorption↗
PubMed1995

X-ray structures of the B-DNA dodecamer d(CGCGTTAACGCG) with an inverted central tetranucleotide and its netropsin complex.

The crystal structures of the B-DNA dodecamer d(CGCGTTAACGCG) duplex (T2A2), with the inverted tetranucleotide core from the duplex d(CGCGAATTCGCG) [A2T2, Dickerson & Drew (1981). J. Mol. Biol. 149, 761-768], and its netropsin complex (T2A2-N) have been determined at 2.3 A resolution. The crystals are orthorhombic, space group P2(1)2(1)2(1), unit-cell dimensions of a = 25.7, b = 40.5 and c = 67.0 A, for T2A2 and a = 25.49, b = 40.87, c = 67.02 A for T2A2-N and are isomorphous with A2T2. The native T2A2 structure, with 70 water molecules had a final R value of 0.15 for 1522 reflections (F > 2sigma), while for the netropsin complex, with 87 water molecules, the R value was 0.16 for 2420 reflections. In T2A2, a discontinuous string of zig-zagging water molecules hydrate the narrow A.T minor groove. In T2A2-N, netropsin binds in one orientation in the minor groove, covering the TTAA central region, by displacing the string of waters, forming the majority of hydrogen bonds with DNA atoms in one strand, and causing very little perturbation of the native structure. The helical twist angle in T2A2 is largest at the duplex center, corresponding to the cleavage site by the restriction enzymes HpaI and HincII. The sequence inversion AATT-->TTAA of the tetranucleotide at the center of the molecule results in a different path for the local helix axis in T2A2 and A2T2 but the overall bending is similar in both cases.

Journal Article↗
PubMed1994

Genetic analysis of regions of the Lactococcus lactis subsp. lactis plasmid pRS01 involved in conjugative transfer.

The genes responsible for conjugative transfer of the 48.4-kb Lactococcus lactis subsp. lactis ML3 plasmid pRS01 were localized by insertional mutagenesis. Integration of the IS946-containing plasmid pTRK28 into pRS01 generated a pool of stable cointegrates, including a number of plasmids altered in conjugative proficiency. Mapping of pTRK28 insertions and phenotypic analysis of cointegrate plasmids identified four distinct regions (Tra1, Tra2, Tra3, and Tra4) involved in pRS01 conjugative transfer. Tra3 corresponds closely to a region previously identified (D. G. Anderson and L. L. McKay, J. Bacteriol. 158:954-962, 1984). Another region (Tra4) was localized within an inversion sequence shown to correlate with a cell aggregation phenotype. Tra1 and Tra2, two previously unidentified regions, were located at a distance of 9 kb from Tra3. When provided in trans, a cloned portion of the Tra3 region complemented Tra3 mutants.

Chromosome Mapping↗