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Biomedical subjects

J Arnold

Publications and source records attributed to J Arnold.

At least 181 records · Page 10Linked to original sources

Current versus historical population sizes in vertebrate species with high gene flow: a comparison based on mitochondrial DNA lineages and inbreeding theory for neutral mutations.

Using inbreeding theory as applied to neutral alleles inherited maternally, we generate expected probability distributions of times to identity by descent for random pairs of mitochondrial genotypes within a population or within an entire species characterized by high gene flow. For comparisons with these expectations, empirical distributions of times to most recent common ancestry were calculated (by conventional mtDNA clock calibrations) from mtDNA haplotype distances observed within each of three vertebrate species--American eels, hardhead catfish, and redwinged blackbirds. These species were chosen for analysis because census population size in each is currently large and because both genetic and life-history data are consistent with the postulate that historical gene flow within these species has been high. The observed molecular distances among mtDNA lineages were two to three orders of magnitude lower than predicted from census sizes of breeding females, suggesting that rate of mtDNA evolution is decelerated in these species and/or that long-term effective population size is vastly smaller than present-day population size. Several considerations point to the latter possibility as most likely. The genetic structure of any species is greatly influenced by historical demography; even for species that are currently abundant, mtDNA gene lineages appear to have been channeled through fairly small numbers of ancestors.

Animals↗

Multiple-dose pharmacokinetics and toleration of intravenously administered cefoperazone and sulbactam when given as single agents or in combination.

The multiple-dose pharmacokinetics and toleration of cefoperazone (3 g every 12 h) and sulbactam (1.5 g every 12 h) were studied when these antimicrobial agents were administered continuously over 7 days as a 15-min infusion of individual agents and as a 3/1.5-g cefoperazone-sulbactam combination. Fourteen male volunteers participated in an open, three-way crossover study of Latin Square design with a 1-week washout period between phases. On days 1 and 7 of each phase, serial serum samples and urine were collected for drug assay over a 12-h period. Hematological and clinical chemistry determinations were made within 10 days before the first antibiotic dose and for each treatment phase just before the first dose, on day 4 of treatment, and within 24 h of the last dose. For cefoperazone as a single agent on days 1 and 7, the average maximal concentration in serum (Cmax) was approximately 430 micrograms/ml, the terminal elimination half-life (t1/2) was 1.8 h, and the average percentage of dose excreted unchanged in the urine (%Ur) was 30%. For sulbactam as a single agent, the Cmax was approximately 90 micrograms/ml, the t1/2 was 1 h, and the %Ur was 89% on days 1 and 7. When comparing individual versus simultaneous drug administration, the only pharmacokinetic alteration observed was a statistically significant but minor (about 10%) decrease in sulbactam renal clearance, on both days 1 and 7, resulting in a similar decrease in total body clearance (CL). The area under the curve, apparent volume of distribution by the area method (V), t1/2, and Cmax were not significantly altered. Although cefoperazone pharmacokinetic parameters were not significantly altered when comparing single-agent to combination drug administration, the area under the curve was slightly lower and CL, nonrenal clearance, and V were modestly higher from day 1 to day 7. Because Cmax and t1/2 were unaffected, these minor day effects would not be of clinical significance. Intravenous administration of cefoperazone and sulbactam given as individual agents compared with the combination did not show pharmacokinetic differences that are likely to produce clinically relevant effects. The combination of cefoperazone and sulbactam was well tolerated, and the safety profile of the combination was similar to that either drug given alone under the conditions of this study.

Adult↗

Lipoprotein lipase in white and brown adipose tissues of exercised rats fed a high-fat diet.

The combined effects of a high-fat-supplemented diet and exercise training on serum lipids as well as on lipoprotein lipase activity in white and brown adipose tissues of the rat were evaluated. Male Wistar rats were fed ad libitum either a stock diet or the stock diet supplemented with food items rich in fat. Half of each dietary group was submitted to daily treadmill running for 35 days. Food intake and final body weight were raised by the high-fat-supplemented diet and lowered by exercise training. Postprandial serum triglycerides were not affected by diet or exercise, whereas the latter decreased total cholesterol in the high-fat group only (14%, P less than 0.01). Total lipoprotein lipase activity in white adipose tissue was elevated (120%, P less than 0.01) by high-fat feeding, and this increase was greatly reduced by concomitant exercise training. In brown adipose tissue, however, the large elevation (104%, P less than 0.01) in enzyme activity brought by the high-fat diet was unaltered by concomitant training. Thus a high-fat-supplemented diet increased lipoprotein lipase activity in both an energy-storing and a heat-producing tissue, and exercise training was able to counteract this effect in white, but not in brown, adipose tissue. These findings support the notion that the regulation of lipoprotein lipase is tissue specific.

Adipose Tissue↗

Lipoprotein lipase in adipose tissues of rats running during cold exposure.

This study evaluated the individual and combined effects of exercise training and intermittent cold exposure of similar energy cost on serum lipids and lipoprotein lipase (LPL) activity on epididymal white (WAT) and interscapular brown (BAT) adipose tissues of the rat. The animals were subjected daily to 2 h of treadmill running at 24 degrees C or for the same period of time at -5 degrees C, with or without exercise, for 28 days. Exercise training lowered serum triglycerides (P less than 0.01), whereas serum cholesterol was reduced by cold exposure (P less than 0.05). Cholesterol lowering occurred in the lipoproteins of lower densities. WAT weight was diminished by both treatments. Exercise training had an overall lowering effect on WAT total LPL activity (P less than 0.05), whereas cold exposure did not affect enzyme activity significantly. Exercise and intermittent cold interacted on BAT weight. Cold increased total BAT LPL activity (P less than 0.03), whereas simultaneous exercise in the cold greatly diminished this effect. Serum insulin levels were not affected by either treatment. Thus, in WAT, intermittent exposure to cold did not have any lasting effect on LPL activity, whereas exercise training decreased the latter. In contrast, exercise did not influence LPL in BAT of rats not exposed to cold but prevented the stimulation of enzyme activity induced by repeated cold exposure. These results support the notion that the regulation of LPL is tissue specific.

Adipose Tissue↗

Huntington disease in Georgia: age at onset.

Age at onset of motor symptoms was collected on 611 persons affected with Huntington disease (HD) among 3,201 persons "at risk" in 108 kindreds. Life-table estimates correcting for truncated intervals of observation (censoring) produced a median age at onset 5 years older than the observed mean. Risk estimates of HD onset for persons at risk, as calculated by life-table methods, were significantly higher for older ages than were estimates based on the observed distribution of onsets. Age-specific incidence was found to be highest at age 35-64 years, a considerably older age interval than suggested by previous estimates. The offspring of affected males had significantly younger onset than did offspring of affected females, and a trend suggesting and excess of paternal descent among juvenile-onset cases was present. Life-table analysis is contrasted with analyses of (a) the observed distribution of age at onset and (b) remote cohorts age 63 or older at the time of data collection. The implications for risk prediction, genetic counseling, and genetic analysis of HD are discussed.

Adult↗

Mono- through hexanucleotide composition of the Escherichia coli genome: a Markov chain analysis.

Several statistical methods were tested for accuracy in predicting observed frequencies of di- through hexanucleotides in 74,444 bp of E. coli DNA. A Markov chain was most accurate overall, whereas other methods, including a random model based on mononucleotide frequencies, were very inaccurate. When ranked highest to lowest abundance, the observed frequencies of oligonucleotides up to six bases in length in E. coli DNA were highly asymmetric. All ordered abundance plots had a wide linear range containing the majority of the oligomers which deviated sharply at the high and low ends of the curves. In general, values predicted by a Markov chain closely followed the overall shape of the ordered abundance curves. A simple equation was derived by which the frequency of any nucleotide longer than four bases in the E. coli genome (or any genome) can be relatively accurately estimated from the nested set of component tri- and tetranucleotides by serial application of a 3rd order Markov chain. The equation yielded a mean ratio of 1.03 +/- 0.94 for the observed-to-expected frequencies of the 4,096 hexanucleotides. Hence, the method is a relatively accurate but not perfect predictor of the length in nucleotides between hexanucleotide sites. Higher accuracy can be achieved using a 4th order Markov chain and larger data sets. The high asymmetry in oligonucleotide abundance means that in the E. coli genome of 4.2 X 10(6) bp many relatively short sequences of 7-9 bp are very rare or absent.

Base Composition↗

The effect of codon usage on the oligonucleotide composition of the E. coli genome and identification of over- and underrepresented sequences by Markov chain analysis.

As shown in the accompanying paper (5), the oligonucleotide composition of the E. coli genome is highly asymmetric for sequences up to 6 bp in length when ranked from highest to lowest abundance. We show here that this largely reflects codon usage because heavily used codons were found in the highly abundant oligomers whereas rarely used codons, with some exceptions, occurred in sequences in low abundance. Furthermore, linear regression analysis revealed a strong correlation between the frequencies of each trinucleotide and its usage as a codon. Dinucleotides are also not randomly distributed across each codon position and the dinucleotide composition of genes that are transcribed but not translated (rRNA and tRNA genes) was highly related to that seen in genes encoding polypeptides. However, 45 tetra-, 8 penta-, and 6 hexanucleotides were significantly over- or underabundant by Markov chain analysis and could not be accounted for by codon usage. Of these underrepresented sequences, many were palindromes, including the Dam methylation site.

Base Sequence↗

The Diogene 4 pi detector at Saturne.

Diogene, an electronic 4 pi detector, has been built and installed at the Saturne synchrotron in Saclay. The forward angular range (0 degree-6 degrees) is covered by 48 time-of-flight scintillator telescopes that provide charge identification. The trajectories of fragments emitted at larger angles are recorded in a cylindrical 0.4-m3 Pictorial Drift Chamber (PDC) surrounding the target. The PDC is inside a 1-T magnetic field; the axis of the PDC cylinder and the magnetic field are parallel to the beam. Good identification has been obtained for both positive and negative pi mesons and for hydrogen and helium isotopes. Multiplicities in relativistic nucleus-nucleus reactions up to 40 have been detected, limited mainly by the present electronics.

Elementary Particles↗

Detraining of exercise-trained rats: effects on energetic efficiency and brown adipose tissue thermogenesis.

Complete energy balance measurements were made in exercise-trained (treadmill running) rats subjected to 27 d of exercise detraining. The 20% difference in body-weight that existed at the end of the training period between sedentary and trained rats was negated by detraining. Detrained rats had twice the body-weight gain of their untrained controls. An elevation (12%) in metabolizable energy (ME) intake (relative to body-weight) was observed in detrained rats while their gross energetic efficiency was augmented by 60%. Energy expenditure, excluding the estimated costs of fat and protein storage, was similar for detrained and untrained rats. Complementing the latter was the finding that thermogenesis in brown adipose tissue, a known energy buffering process, was also similar. Elevated ME intake (relative to body-weight) largely contributed to the increased energetic efficiency of detrained rats.

Adipose Tissue, Brown↗

Definition and properties of disequilibrium statistics for associations between nuclear and cytoplasmic genotypes.

We define and establish the interrelationships of four components of statistical association between a diploid nuclear gene and a uniparentally transmitted, haploid cytoplasmic gene: an allelic (gametic) disequilibrium (D), which measures associations between alleles at the two loci; and three genotypic disequilibria (D1, D2, D3), which measure associations between two cytotypes and the three respective nuclear backgrounds. We also consider an alternative set of measures, including D and the residual disequilibrium (d). The dynamics of these disequilibria are then examined under three conventional models of the mating system: (1) random mating; (2a) assortative mating without dominance (the "mixed-mating model"); and (2b) assortative mating with dominance ("O'Donald's model"). The trajectories of gametic disequilibria are similar to those for pairs of unlinked nuclear loci. The dynamics of genotypic disequilibria exhibit a variety of behaviors depending on the model and the initial conditions. Procedures for statistical estimation of cytonuclear disequilibria are developed and applied to several real and hypothetical data sets. Special attention is paid to the biological interpretations of various categories of allelic and genotypic disequilibria in hybrid zones. Genetic systems for which these statistics might be appropriate include nuclear genotype frequencies in conjunction with those for mitochondrial DNA, chloroplast DNA, or cytoplasmically inherited microorganisms.

Alleles↗

Protein, lactose and fat concentration of breast milk of mothers of term and premature neonates.

The protein, lactose and fat concentrations in the milk of seven mothers giving birth at term and six mothers giving birth prematurely were determined. Samples were obtained during the first 31 days of lactation. The protein, lactose and fat concentrations of preterm milk were found to be similar to those of fullterm milk over this period. For both term and preterm groups, protein concentration decreased with increasing age, while lactose concentration increased. Fat concentration did not show a consistent pattern of change in the preterm group, but tended to increase with advancing age in the term group.

Adult↗

Exercise during intermittent cold exposure prevents acclimation to cold rats.

1. Energy balance and brown adipose tissue growth were examined in four groups of male Wistar rats: (i) sedentary, living at 24 degrees C (warm), (ii) exercise-trained, 2 h daily, living at 24 degrees C, (iii) living at 24 degrees C but exposed to -5 degrees C, 2 h daily and (iv) living at 24 degrees C but exercise-trained while being exposed to -5 degrees C, 2 h daily. 2. Cold exposure during exercise training appeared to have little additional influence on body composition following 28 days of treatment; body mass gain, in addition to protein and fat gains, of exercised cold-exposed rats were similar to the gains observed in exercised warm-exposed control animals. However, in sedentary cold-exposed rats protein, fat and body mass gains were significantly lower than the gains measured in sedentary rats not exposed to cold. 3. Metabolizable energy intake, expressed mass-independently, was similar in sedentary warm-exposed rats and both groups of animals that were exercise-trained. Metabolizable energy intake was increased almost 15% in sedentary cold-exposed rats. 4. Energy expenditure (mass independent), excluding the net cost of exercise training, was not different in sedentary warm-exposed and exercised rats; energy expenditure was almost 20% higher in sedentary cold-exposed rats. 5. Total protein and deoxyribonucleic acid (DNA) contents of brown adipose tissue were more than doubled in sedentary rats exposed to cold; protein and DNA levels were similar among the other three groups of rats. 6. Treadmill running during daily, 2 h exposure at -5 degrees C appears to prevent the cold acclimation responses that occur in sedentary rats receiving similar cold exposure.

Acclimatization↗

Unaltered regulatory thermogenic response to dietary signals in exercise-trained rats.

Thermogenic response to ingestion of high-fat diet was investigated in four groups of male rats, two groups being exercise trained and two remaining sedentary. One sedentary and one trained group each received a high-fat dietary supplement in addition to the stock diet. After 35 days, body energy and protein and fat contents were determined. Results indicate that exercise reduced metabolizable energy (ME) intake by 9 and 18% in stock- and high-fat-fed trained rats, respectively. Compared with stock-fed rats, ME intake was elevated 31 and 18% in sedentary and trained high-fat-fed rats, respectively. Exercise also affected energy gains; trained rats deposited almost 60% less energy than controls. Exercise largely decreased both fat and protein contents of rats, whereas the high-fat supplement enhanced fat deposition. Energy expenditure, excluding exercise cost, was calculated on a mass-independent basis and was revealed to be similar in appropriately matched (diet) trained and sedentary rats. High-fat feeding induced increases in expenditure assumed to be due to enhanced brown adipose tissue (BAT) regulatory diet-induced thermogenesis. Conversely, exercise did not affect further the regulatory thermogenic response of BAT to stimuli originating from high-fat diet. Excluding physical activity, energy expenditure components in sum (expressed mass independently), in high-fat- and stock-fed rats, appear unaltered by exercise training.

Adipose Tissue, Brown↗

Intra-oral effects on acid-softened enamel of NaF lozenges administered in divided daily doses.

The purpose of this investigation was to study the intra-oral effects of multiple daily applications of NaF lozenges upon acid-softened enamel. Bovine enamel slabs were softened with 0.1 mol/L lactate buffer at pH 4.0 for 14 hrs and subsequently mounted in a mandibular removable Hawley appliance. Control slabs were worn for seven days by eight adult male subjects who brushed their natural dentition daily with a fluoride-free dentifrice. Test slabs were exposed to one 0.55-mg NaF lozenge (0.25 mg F) 4x/day for seven days and the natural dentition brushed with a fluoride-free dentifrice. The efficacy of 0.25-mg F lozenges used 4x/day over that of a 1-mg F lozenge administered 1x/day was established by a pilot study with two subjects. Microhardness testing was performed after intra-oral exposure (IOE) and following immersion in 0.01 mol/L lactate buffer containing Ca and PO4 for 24 hrs at a pH of 4.0. Fluoride uptake was measured on separate control and test slabs after KOH wash and after acid-resistance-testing (ART). Recovery of microhardness following IOE was 40.9% for controls and 53.9% for treated slabs, while control slabs retained 1.3% resistance to ART, compared with 25.6% for test slabs. The F content of the control slabs was significantly less than that of lozenge-treated and lozenge-treated-ART slabs throughout the depth of the lesion. The F content of the lozenge-treated-ART slabs was significantly less than that of the lozenge-treated slabs only at the 0-5-microns depth.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Effects of exercise and intermittent cold exposure on shivering and nonshivering thermogenesis in rats.

The effects of both exercise training and intermittent cold acclimation on heat production (shivering and nonshivering thermogenesis (NST)) in rats were studied. Warm-acclimated rats (housed at 24 degrees C, WA) and intermittently cold-acclimated rats (exposed daily to -5 degrees C for 2 h, CA) were forced to run (25 m.min-1 for 1 h) every day (WA-T and CA-T). WA and CA left sedentary (WA-S and CA-S) served as controls. Norepinephrine (NE)-induced thermogenic capacity assessed from the increment of oxygen consumption (VO2) and colonic temperature (Tc) were measured 4 weeks after commencing acclimation and exercise training. The thermogenic capacity was greater in CA than in WA. However, in WA, WA-T responded to NE less than WA-S, whereas the response of CA-T and CA-S did not differ. Wet weight of interscapular brown adipose tissue (IBAT) and its protein (and dry matter--regarded to be highly representative of protein) content were larger in CA than in WA. Respective sedentary and exercised groups of rats had similar IBAT protein (and dry matter) content although tissue weight was lighter in WA-T than in WA-S. Lipid content of IBAT was also larger in CA than in WA. IBAT of WA-T had less lipid compared to that of WA-S while no difference was seen between CA-S and CA-T. Shivering activity during acute cold (4 degrees C) exposure was less in CA compared to WA and there was no difference between respective groups of exercised and sedentary rats. Propranolol, a blocker of NE-dependent NST, eliminated the difference in shivering among these four groups. When exposed to severe cold (-10 or -20 degrees C), the fall in Tc of rats fasted for 18 h was greater in WA than in CA. CA-T showed a greater decrease in Tc than CA-S during -20 degrees C exposure while it did not differ during -10 degrees C exposure. On the other hand, Tc of WA-T and WA-S did not differ significantly during either cold exposure period. These results suggest that exercise training in rats housed at 24 degrees C suppresses NE-dependent NST whereas another nonshivering thermogenic mechanism (NE-independent) may compensate this suppression. However, NE-dependent NST of WA-S and WA-T did not parallel protein (dry matter) content of IBAT; no difference existed in IBAT protein between these two groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Acclimatization↗

Retinal microembolism during cardiopulmonary bypass demonstrated by fluorescein angiography.

Fluorescein angiography was used to study retinal microvascular perfusion in 20 patients undergoing coronary artery surgery. Colour retinal photographs and fluorescein angiograms were obtained preoperatively and at 5-14 days postoperatively. In 10 patients retinal fluorescein angiograms were also obtained intraoperatively during cardiopulmonary bypass, and all were found to have retinal microvascular occlusions after 40-160 min of extracorporeal circulation. 3 patients had in addition focal leakage of fluorescein, and 6 had foci of abnormal drainage of dye. These changes are consistent with retinal microembolism, and appeared to have resolved by the time of the postoperative study. No new pathological features appeared in the retina after surgery. Intraoperative fluorescein angiography of the retina may prove valuable for investigation of cerebrovascular microembolism in the territory of the internal carotid artery during cardiopulmonary bypass in man.

Aged↗

A comprehensive package for DNA sequence analysis in FORTRAN IV for the PDP-11.

A computer package written in Fortran-IV for the PDP-11 minicomputer is described. The package's novel features are: software for voice-entry of sequence data; a less memory intensive algorithm for optimal sequence alignment; and programs that fit statistical models to nucleic acid and protein sequences.

Base Sequence↗