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PubMed2000

Volitional ethanol consumption affects overall serotonin metabolism in Syrian golden hamsters (Mesocricetus auratus).

Methods were established for the determination of serotonin (5-HT)(1) metabolites 5-hydroxyindole-3-acetic acid (5-HIAA) and 5-hydroxytryptophol (5-HTOL) in the urine of Syrian golden hamsters (Mesocricetus auratus) and used to study the effect of volitional ethanol consumption on overall 5-HT metabolism in this ethanol-preferring rodent. The basal levels of 5-HIAA and 5-HTOL in 24-h urine of ethanol-naive hamsters were 300 +/- 101 and 4.96 +/- 1. 06 nmol (n = 8), respectively. Given free choice between water and a 15% ethanol solution, these hamsters chose to consume increasing amounts of ethanol. The increase was accompanied by a concomitant decrease in urine 5-HIAA and increase in urine 5-HTOL, indicating that volitional ethanol intake diverted part of the 5-HT metabolic flux from an oxidative into a reductive pathway. In a separate experiment, the amounts of ethanol consumed by and blood ethanol concentrations attained in ethanol-drinking golden hamsters were determined at 5 different time intervals between 6 PM and 7 AM when most feeding activities occurred. Except in the first hour after lights were turned off, ethanol was consumed at a relatively even pace throughout the night (2-3 g/kg/3 h) and blood ethanol levels were maintained at the low mM range which rarely exceeded 2 mM. These results suggest that the biochemical pathway that catalyzes 5-HT metabolism is extremely sensitive to ethanol and can play an important role in mediating the reported clinically beneficial action of a low concentration of ethanol during alcohol detoxification.

Animals↗
PubMed2000

Hox C cluster genes are dispensable for overall body plan of mouse embryonic development.

Hox genes encode transcription factors which provide positional information during morphogenesis along the body axis; genetic interaction among Hox genes is thought to be necessary for correct pattern formation. One of the most curious features of the 39 vertebrate Hox genes is that they form four clusters each composed of several genes paralogous between clusters. This raises the question are all four clusters necessary for the development of vertebrates and, if so, what is the function of each cluster? To provide an answer to this question, we prepared Hox C cluster null mice utilizing the Cre-loxP system. Hox C cluster null mice, lacking all nine Hox C genes, die at the time of birth; however, the mutant pups develop to this stage with minor transformations. This development shows that the Hox C genes are dispensable for the overall body plan of mouse embryogenesis. Furthermore, transformations observed in the skeletal system of the Hox C cluster null mice are milder than those observed in the Hoxc-9 null mice, providing further evidence that at least some genes within a cluster exhibit interaction functions with each other.

Animals↗
PubMed1996

Overall informativity, OI, in DNA polymorphisms revealed by inter-Alu PCR: detection of genomic rearrangements.

We studied two systems of multilocus markers revealed by PCR using primers directing amplification between Alu repeats in a tail-to-tail orientation. Genomic polymorphisms were detected as the presence or absence of the electrophoretic bands representing DNA fragments of a given length. A total of 104 such fragments segregating as Mendelian markers in a panel of eight CEPH families were analyzed by two-point linkage analysis. Fifty-one of these fragments were localized with respect to CEPH markers; they represented 33 loci, 7 of which were multiallelic. Locus-specific oligonucleotides were developed and used as hybridization probes to identify the mapped loci within a complex pattern of inter-Alu PCR products. A great proportion of inter-Alu PCR polymorphisms represented length variants within amplified DNA segments, while others were presumably due to mutations within the priming sites. To describe the expected number of informative loci per typing experiment we introduced a parameter called overall informativity (OI), which provides a single measure of the multiplex ratio and the informativity of markers contributing to a multilocus system (OI of a single locus is equivalent to its heterozygosity and cannot exceed 0.5 for a biallelic codominant marker). High OI values (5.8 and 11.5) of the two presented systems of inter-Alu PCR markers of random chromosomal distribution render them suitable for mapping genomic rearrangements such as genomic deletions in tumoral tissues. This was illustrated by the detection of loss of heterozygosity in the 9q22-qter region in sporadic colon cancer.

Animals↗
PubMed2000

Basicranial influence on overall cranial shape.

This study examines the extent to which the major dimensions of the cranial base (maximum length, maximum breadth, and flexion) interact with brain volume to influence major proportions of the neurocranium and face. A model is presented for developmental interactions that occur during ontogeny between the brain and the cranial base and neurocranium, and between the neurobasicranial complex (NBC) and the face. The model is tested using exocranial and radiographic measurements of adult crania sampled from five geographically and craniometrically diverse populations. The results indicate that while variations in the breadth, length and flexion of the cranial base are mutually independent, only the maximum breadth of the cranial base (POB) has significant effects on overall cranial proportions, largely through its interactions with brain volume which influence NBC breadth. These interactions also have a slight influence on facial shape because NBC width constrains facial width, and because narrow-faced individuals tend to have antero-posteriorly longer faces relative to facial breadth than wide-faced individuals. Finally, the model highlights how integration between the cranial base and the brain may help to account for the developmental basis of some morphological variations such as occipital bunning. Among modern humans, the degree of posterior projection of the occipital bone appears to be a consequence of having a large brain on a relatively narrow cranial base. Occipital buns in Neanderthals, who have wide cranial bases relative to endocranial volume, may not be entirely homologous with the morphology occasionally evident in Homo sapiens.

Adult↗
PubMed1993

Physiological relevance of the overall delta H of oxygen binding to fetal human hemoglobin.

Human fetal hemoglobin is known to display, at 20 degrees C, a lower affinity than human adult hemoglobin for oxygen when both proteins are in the absence of organic phosphates. The physiologically important reverse situation is achieved at 37 degrees C upon addition of 2,3-bisphosphoglycerate (DPG), whose lower effect on fetal hemoglobin is related to some amino acid substitutions present in gamma-chains. However, the difference in oxygen affinity observed at 37 degrees C is not solely due to the different modulation power of DPG with respect to adult and fetal hemoglobins. In fact, the results presented here reveal new aspects linked to the interplay of temperature and organic phosphates. In particular, the lower effect of DPG on fetal hemoglobin renders almost identical the oxygen affinity of the two hemoglobins at 20 degrees C, abolishing the difference observed in the absence of the effector. Successively on going from 20 degrees C to 37 degrees C, by virtue of the lower overall heat of oxygenation (delta H) displayed by fetal hemoglobin when in the presence of DPG, adult hemoglobin shows a lower oxygen affinity, as it should if oxygen has to be transferred from maternal to fetal blood.

2,3-Diphosphoglycerate↗
PubMed1998

Vibration-Internal Rotation-Overall Rotation Interactions in CH3OH

The zeroth order kinetic energy is developed for the vibrating-internally rotating-rotating CH3OH molecule using the general theory of Guan and Quade for large amplitude internal motion-vibration-rotation interactions in molecules. The R and T transformations are applied, respectively, to separate internal rotation from the other vibrations and overall rotation from the other vibrations in zeroth order. All zeroth order kinetic energy coefficients are calculated from the geometry and atomic masses of the CH3OH molecule. The physical significance of the two transformations is discussed in detail. This paper reports the results of the first segment of the many segments necessary in the calculations for full solution of the problem. Copyright 1998 Academic Press.

Journal Article↗
PubMed1999

Vibration-Internal Rotation-Overall Rotation Interactions in CH(2)DOH and CHD(2)OH.

The zeroth-order kinetic energy is developed for the vibrating-rotating-internally rotating CH(2)DOH and CHD(2)OH molecules using the general theory of Guan and Quade for the vibration-rotation-large amplitude internal motion interactions in molecules. A T transformation is applied to obtain the necessary (G(-1))(0) vibrational matrix elements in the kinetic energy for the R transformation that separates the internal rotation from the 3N-7 other vibrations. Then, a second T transformation is used to separate rotation from the 3N-7 other vibrations in zeroth order in the kinetic energy. The overall rotation and internal rotation remain coupled in zeroth order. All zeroth-order kinetic energy coefficients are calculated from the molecular structure and masses for the methyl alcohol molecules. The physical significance of the transformations is discussed in detail. This paper reports the results of the first segment of the three segments that are necessary in the calculation of the full solution to the problem. Copyright 1999 Academic Press.

Journal Article↗
PubMed1990

The effect of epinephrine on oxygen consumption, overall energy metabolism, and substrate utilization in rats.

In this study the influence of epinephrine (E) on oxygen consumption, overall energy metabolism, and substrate utilization in rats has been investigated. Therefore E was infused at rates of 20, 35, and 50 ng/min for 40 min. Infusion of the solvent, saline, served as control experiment. Before, during, and after the infusion, VO2, as parameter for total metabolism, and RQ, as parameter for substrate utilization, were determined using an open circuit. In addition blood samples were taken for determination of blood glucose, plasma free fatty acids (EFA) and plasma insulin concentrations. The results show a rise in VO2 and blood glucose during infusion of E. Plasma FFA concentrations were elevated during infusion of E and of saline. Plasma insulin decreased when E was administered. RQ values were increased when E was infused at rates of 35 and 50 ng/min. The results suggest that E can influence the ratio in which glucose and FFA are utilized. This influence seems to be excerpted indirectly by influencing the availability of the substrates, rather than directly, by influencing utilization.

Animals↗
PubMed1990

Low-cost mass screening as a means of reducing overall mortality from breast cancer.

Mammography is a screening method that has been proven effective and could significantly reduce the overall mortality from breast cancer if it were more widely applied. The challenge to radiology is to provide sufficient competent personnel and adequate facilities such that reproducibly optimal screening mammography, accurately interpreted at the lowest possible cost, is made widely available.

Breast Neoplasms↗
PubMed1994

AIDS-free survival and overall survival in HIV infection: the new CDC classification system (1993) for HIV disease and AIDS.

The clinical history of 1538 HIV positive patients was analyzed on the basis of the new CDC classification system of HIV disease and AIDS. This classification system combines three CD4 cell categories (1, 2, and 3) with three clinical categories (A, B, and C) into nine subgroups A1-C3. We examined the overall survival for all subgroups and the AIDS-free survival for subgroups A1-B3. AIDS-free survival for patients in subgroups A1, A2, and B1 was considerably longer than survival in patients from subgroups A3, B2, and B3 (P < 0.0001). According to these findings, the new CDC classification system could be simplified into three stages, stage I and II comprising the above mentioned six subgroups, and stage III comprising clinical AIDS defining categories C1, C2, and C3. These three stages correspond to different periods in the management of HIV positive patients, i.e., period of observation, period of prophylaxis, and period of treatment.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Contribution of differentiated ratings of perceived exertion to overall exertion in women while swimming.

The purpose of this study was to identify, using multiple regression analysis, the contribution of differentiated ratings of perceived exertion to overall exertion (RPEO) in women while swimming. Ten female subjects swam at submaximal and maximal intensities and the variables measured included oxygen uptake (VO2), heart rate (fc), ventilation (VE), breathing frequency, tidal volume, blood lactate concentration ([la-]b), RPEO, and four differentiated RPE. These four differentiated RPE were cardiac frequency rating (RPEC), respiratory frequency rating (RPER), arm rating (RPE(arm)), and leg rating (RPE(leg)). These variables used the following equation based on VO2 - R = a + c.(S-b)n, where R was the response to increasing exercise intensity (S) and a, b, and c were constants. The exponents (n) of fc, VE and [la-]b were approximately 1.0, 2.0 and 3.3, respectively. The estimated exponents of RPEO, RPEC, RPER, RPE(arm) and RPE(leg) were approximately 2.4, 2.3, 2.2, 2.5 and 2.5, respectively. There was a highly significant relationship between the four differentiated RPE and their associated physiological responses. The results of this study showed that these interrelationships were clearly delineated. As the percentage maximal oxygen uptake (% VO2max) increased, the major contributing factor to RPEO changed. The RPEC was found to be the main contributing factor from 20% to 45% VO2max, but ceased to contribute beyond 50% VO2max. Above 45% VO2max, RPE(arm) was the major influence, and RPER was the secondary influence from 66% to 96% VO2max. The RPE(leg) was the secondary contributing factor only from 27% to 35% VO2max. It was concluded that differentiated RPE contribution was dependent upon the intensity of exercise in women while swimming.

Adult↗
PubMed1994

Centromere promoter factors (CPF1) of the yeasts Saccharomyces cerevisiae and Kluyveromyces lactis are functionally exchangeable, despite low overall homology.

The KlCPF1 gene, coding for the centromere and promoter factor CPF1 from Kluyveromyces lactis, has been cloned by functional complementation of the methionine auxotrophic phenotype of a Saccharomyces cerevisiae mutant lacking ScCPF1. The amino-acid sequences of both CPF1 proteins show a relatively-low overall identity (31%), but a highly-homologous C-terminal domain (86%). This region constitutes the DNA-binding domain with basic-helix-loop-helix and leucine-zipper motifs, features common to the myc-related transcription factor family. The N-terminal two-thirds of the CPF1 proteins show no significant similarity, although the presence of acidic regions is a shared feature. In KlCPF1, the acidic region is a prominent stretch of approximately 40 consecutive aspartate and glutamate residues, suggesting that this part might be involved in transcriptional activation. In-vitro mobility-shift experiments were used to establish that both CPF1 proteins bind to the consensus binding site RTCACRTG (CDEI element). In contrast to S. cerevisiae, CPF1 gene-disruption is lethal in K. lactis. The homologous CPF1 genes were transformed to both S. cerevisiae and K. lactis cpf1-null strains. Indistinguishable phenotypes were observed, indicating that, not withstanding the long nonconserved N-terminal region, the proteins are sufficiently homologous to overcome the phenotypes associated with cpf1 gene-disruption.

Amino Acid Sequence↗
PubMed1975

X-ray small-angle studies of the pyruvate dehydrogenase core complex from Escherichia coli K-12. I. Overall structure of the core complex.

The pyruvate dehydrogenase core complex from E. coli K-12, defined as the multienzyme complex which can be obtained with a unique polypeptide chain composition, has been investigated in solution with the X-ray small-angle technique. The molecular mass of the core complex of 3.78-10(6) daltons verifies the ratio of polypeptide chains of 16:16:16 of the three enzyme components, pyruvate dehydrogenase, dihydrolipoamide transacetylase, and dihydrolipoamide dehydrogenase, present in the complex. In connection with the values obtained for the radius of gyration (156.5A), volume (1.07(7) A3) and amount of solvent associated with the complex (1.03 g/g) a loose packing of subunits in the complex has to be assumed. The maximum diameter of the core complex of 433 A, as determined from the correlation function, corroborates the large extension of the complex. The comparison of experimental and theoretical scattering curves reveals a relatively isometric overall shape of the core complex.

Escherichia coli↗
PubMed1989

Overall nutrient intake of preschool hyperactive and normal boys.

Studies examining the relationship between sugar intake of hyperactive children and behavior problems have reported inconsistent results. We hypothesized that if the problem behaviors of attention deficit-disordered children with hyperactivity (ADDH) are exacerbated by food, then this might be due to differences in their background nutrition relative to non-ADDH children. Parents and day care workers of 24 ADDH and 27 non-ADDH preschool-aged boys were trained to keep food diaries for 21 days. Analysis of the last 14 days for each child revealed no differences in overall nutrient intake between the two groups. On the other hand, for 5 ADDH and 3 non-ADDH children the within-subject correlations between daily behavior and sugar intake were significant. We concluded that nutrition-behavior interactions are more likely a function of idiosyncratic sensitivities, rather than a general tendency for ADDH children to eat differently from non-ADDH children.

Attention Deficit Disorder with Hyperactivity↗
PubMed1992

Assessment of a model for overall left ventricular three-dimensional motion from MRI data.

In this paper we present a complete methodology to evaluate a model for overall three-dimensional (3D) motion of the human left ventricle (LV) from MRI data. The left ventricular motion is approximated by a linear model associated with an affine transformation to determine parameters for non-rigid motion of the LV. The proposed method has been applied to a normal patient and to a patient with cardiac disease. Results obtained show that the linear model provides a fairly good approximation of normal left ventricular motion, whereas serious cardiac disease produces abnormal motion, yielding altered model performances.

Heart Diseases↗
PubMed1993

Overall signal sequence hydrophobicity determines the in vivo translocation efficiency of a herpesvirus glycoprotein.

We have described three mutant strains of Pseudorabies virus that contain mutations in the signal sequence coding region of a nonessential envelope glycoprotein, gIII. The alterations disrupt, truncate, or eliminate the hydrophobic core domain of the signal sequence. Each mutant was assayed for its ability to promote the translocation of gIII across the endoplasmic reticulum membrane and the subsequent localization of the mature form of the glycoprotein to the infected cell surface or the virus envelope. Our results confirm and extend findings in other systems that the overall hydrophobicity of the signal sequence core region is a major determinant of translocation efficiency. We were unable to correlate simply the length of the core or the average hydrophobicity of core residues with export efficiency. Because our work involved the use of infectious virus mutants, we were able to identify a virus defect associated with a complete block in gIII export. This defect will facilitate a pseudo-reversion analysis of gIII signal sequence function.

Amino Acid Sequence↗
PubMed1995

The overall safety of oral roxithromycin in paediatric clinical studies.

In two multicentre, non-comparative studies, a total of 477 children, aged 2 months to 15 years, suffering from respiratory tract infections or skin and soft tissue infections were treated with roxithromycin (50 mg sachets). The mean duration of treatment was 9 days and the mean daily dose was 6 mg/kg/day administered b.i.d. The overall safety of roxithromycin was assessed by analysing the adverse events reported by the patients or investigators, the discontinuation of treatment because of adverse events, and the laboratory data. Adverse events reported by 20 (4%) children were considered to be possibly drug related. These adverse events were mainly digestive in nature and mild or moderate in severity. Treatment was discontinued because of adverse events in six (1%) children. Analysis of laboratory data revealed a few variations without any clinical significance.

Administration, Oral↗
PubMed1999

Assessment of aortic pressure power components and their link to overall elastic and resistive arterial properties.

This paper reviews the analytical expressions for in-phase and quadrature aortic power components associated with the real and imaginary parts of aortic input admittance, respectively. It is shown that active power Wact, and its steady, Wstdy, and pulsatile, Wpuls, components logically follow from in-phase power. Reactive power follows from quadrature power only for sinusoidal signals. The definition of reactive power indexes for real aortic pressures and flows requires extreme care. The link between overall arterial properties and pressure power components (and indexes) is investigated, making use of a three-element windkessel model and ascending aortic pressure and flow data taken from eight anaesthetised dogs, under basal state and after treatment with a vasoconstrictor (methoxamine). Seven dogs are normotensive in the baseline state (NBA cases, n = 7), the average (+/- SE) of mean pressure being 86.5 +/- 5.2 mmHg. The eighth dog has a baseline mean pressure of 134 mmHg and is considered to be hypertensive. The two experimental cases from this dog are grouped with those from the other seven dogs after vasoconstriction, to form the NVC + H group (n = 9). On average, fitting the model to the experimental data yields a 100% increase (p < 0.05) in total peripheral resistance, a 63% decrease (p < 0.01) in total arterial compliance and a 10% decrease (p > 0.05) in aortic characteristic impedance, from the NBA group to the NVC + H. Correspondingly, the peak-to-peak amplitude of quadrature power shows a 69% increase (p < 0.02). Wact, Wstdy, and Wpuls show a 28% increase (p > 0.05), a 40% increase (p < 0.02) and a 43% decrease (p > 0.05), respectively. Energetic efficiency of the arterial system, Eart = 1 - (Wpuls/Wact), increases by 8% (p < 0.02). From analysis of the estimates of power components and arterial parameters in relation to low-frequency phase angles of aortic impedance, it is concluded that the decrease in total arterial compliance with increasing pressure reduces the power lost in pulsation. This happens at the expense of an increase in quadrature power and absolute values of related reactive power indexes.

Animals↗