Biomedical subjects

J Arnold

Publications and source records attributed to J Arnold.

At least 73 records · Page 4Linked to original sources

PubMed1997

In vitro reconstruction of the Aspergillus (= Emericella) nidulans genome.

A physical map of the 31-megabase Aspergillus nidulans genome is reported, in which 94% of 5,134 cosmids are assigned to 49 contiguous segments. The physical map is the result of a two-way ordering process, in which clones and probes were ordered simultaneously on a binary DNA/DNA hybridization matrix. Compression by elimination of redundant clones resulted in a minimal map, which is a chromosome walk. Repetitive DNA is nonrandomly dispersed in the A. nidulans genome, reminiscent of heterochromatic banding patterns of higher eukaryotes. We hypothesize gene clusters may arise by horizontal transfer and spread by transposition to explain the nonrandom pattern of repeats along chromosomes.

Aspergillus nidulans↗

PubMed1997

[Endoscopic study of the small intestine with push enteroscopy. A prospective study].

OBJECTIVE: To evaluate whether push enteroscopy of the small bowel (PES), undertaken after extensive previous investigations in suspected intestinal bleeding from an uncertain site, chronic diarrhoea or lymphoma of the small intestine, contributes to the diagnosis, and to ascertain the results of PES and its clinical significance. PATIENTS AND METHODS: 56 consecutive patients (29 men, 27 women; mean age 63 years) were investigated prospectively. The main indications for PES were the search for the source of intestinal bleeding in 79% of patients (group A), chronic diarrhoea or tropical sprue in 16% (group B) and search for tumour of lymphoma in 5% (group C). PES was always performed in fasting patients under sedation/analgesia using a video PES, which contrary to catheter enteroscopy provides a channel for intervention. RESULTS: In group A 27% of patients were found to have lesions, in particular angiodysplasias, or (in once case) leiomyoma. Half of these patients were successfully treated endoscopically without later surgical intervention being required (mean follow-up of six months). In the other half operation became necessary, either because the disease itself indicated it or the bleeding persisted, the source being in the more distant small intestine and thus not accessible to endoscopic intervention: only 50% of the length of the small intestine proved to be within reach of the instrument. No abnormalities were discovered in patients of groups B and C. CONCLUSION: In cases of gastrointestinal bleeding from an uncertain source PES should be performed first, because in many cases it may obviate surgical intervention. But PES seems to contribute little of diagnostic value in other indications.

Adult↗

PubMed1997

Editorial

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Journal Article↗

PubMed1997

Indirect scatter laser photocoagulation to subfoveal choroidal neovascularization in age-related macular degeneration.

BACKGROUND: Occult choroidal neovascularization (CNV), poorly defined on fluorescein angiography, is present in the majority of patients with exudative complications of age-related macular degeneration. For patients who present with this type of subfoveal CNV but who have useful visual acuity, no form of treatment is of proven benefit. Accordingly, a pilot randomized trial of indirect laser treatment was performed. The rationale of this treatment was to inhibit the CNV through laser-induced effects on the retinal pigment epithelium. METHODS: Patients with occult subfoveal CNV without retinal pigment epithelial detachment and with visual acuity of 20/200 or better were randomized to treatment or control groups. A grid of laser burns was applied to the macula beyond the area of serous retinal detachment and of angiographically defined occult CNV. RESULTS: After an average follow-up of 38 months, there was no difference in mean final visual acuity (0.12 treated, 0.14 control) or clinical outcome between treated and untreated groups. Fluorescein angiography showed gradual enlargement in the occult CNV in 58% of eyes in both groups. A decrease in visual acuity to worse than 20/200 (54% of treated, 50% of control eyes) was associated with ingrowth of well-delineated CNV (6 treated, 7 control eyes) or progression to a fibroglial or atrophic scar (11 treated, 8 control eyes). CONCLUSIONS: No benefit was demonstrated for scatter photocoagulation of the macula in patients with age-related macular degeneration and occult subfoveal CNV with initially good visual acuity. There were, however, no complications related to treatment.

Aged↗

PubMed1997

Longitudinal study of plasma cortisol and 17-hydroxyprogesterone in very-low-birth-weight infants during the first 16 weeks of life.

There are few published data on plasma cortisol and 17-hydroxyprogesterone (17-OHP) in very-low-birth-weight (VLBW) infants beyond the 1st week of life. We therefore measured plasma cortisol and 17-OHP longitudinally in 26 infants (median birth weight 930 g, median gestational age 28 weeks) from 1 to 16 postnatal weeks to document normative values. We also examined the effect of clinical state on plasma cortisol and 17-OHP levels. Median plasma cortisol decreased with postnatal age from 1 to 8 weeks (110 vs. 60 nmol/l; p = 0.0007) and with postconceptional age from 25 to 36 weeks (104 vs. 47 nmol/l; p = 0.002). Median plasma 17-OHP decreased with postnatal age from 1 to 16 weeks (17.0 vs. 7.1 nmol/l; p < 0.0005) and also with postconceptional age from 25 to 42 weeks (21.1 vs. 7.1 nmol/l; p < 0.0005). Plasma cortisol was not influenced by the clinical state. Median plasma 17-OHP was significantly higher for 'unwell' versus 'well' infants at 5-8 weeks postnatal age (23.0 vs. 12.5 nmol/l; p = 0.012) but not at other postnatal age intervals. These data provide information on adrenocortical function in VLBW infants during the first 4 months of life.

17-alpha-Hydroxyprogesterone↗

PubMed1997

Ventilatory-control abnormalities in familial sleep apnea.

The role of ventilatory-control abnormalities in predisposing to familial sleep-disordered breathing (SDB) was assessed in 31 subjects 28 +/- 10 yr of age (mean +/- SD). Subjects with (n = 10) and without SDB (n = 12) were recruited from 13 families having two or more members with SDB. Nine age- and gender-matched controls were recruited from families having no member with SDB. Respiratory responses to eucapnic hypoxia, and ventilatory and occlusion pressure responses to hyperoxic hypercapnia with and without added resistive loads (6.5 cm H2O/L/s), were assessed through rebreathing. Age, FEV1, and FVC did not differ among the groups. Hypoxic responses (delta VE/delta SaO2) were significantly lower among the first-degree relatives of SDB families than among controls (-0.76 +/- 0.47 L/min/% SaO2, and -1.32 +/- 0.92 L/min/% SaO2, respectively, p < 0.05). Respiratory responses to hypercapnia during unloaded conditions were similar among the groups. With resistive loading, inspiratory impedance, as measured through the relationship of mouth occlusion pressure (P100) to inspiratory flow (VT/TI), increased with increasing hypercapnia to a greater extent in members of SDB families than in controls (0.169 +/- 0.054 cm H2O/L/min versus 0.122 +/- 0.051, respectively, p < 0.05). These data suggest that familial SDB may be based partly on a familial abnormality in ventilatory control associated with blunting of the hypoxic ventilatory response. The greater increase in impedance during inspiratory loading in members of affected families also suggests a propensity for dynamic airway narrowing.

Adult↗

PubMed1997

[Technical adaptation of impulse oscillometry to special research conditions].

The technical adaptation of the Impulse-Oscillometry (IOS) to different conditions of measurement allows a wide range of applications so that even questions of peripheral user groups using lung function tests can be answered. Thus, the variable connection of the IOS head via fold hose opens the field of bedside measurements and additional applications in pediatrics, intensive care and veterinary medicine. Rhinomanometric examinations are possible with little expenditure and high practicability using nasal tips.

Adult↗

PubMed1997

[Diurnal profile of impulse oscillometric impedance in healthy subjects].

Diurnal profiles of impulse oscillometry during 24 hours in 3 hour intervals in sitting and lateral lying position have been studied in 20 healthy female and male probands 10-67 years of age. Approximating the profiles by a sine-cosine-function the amplitude of resistance was found up to 3, that of reactance up to 1 hPa/l/s in single cases, preferably for end-expiratory values and for the resistance-flow- and the resistance-volume-gradients, more pronounced in lying than in sitting position. The daytime reaching maxima of resistance and minima of reactance is different in single individuals. Single persons with obviously high vitality or sensibility showed very high amplitudes reproducible within IOS measuring limits of 0.2 hPa/l/s after 6 months.

Adolescent↗

PubMed1997

Thermogenic, hormonal and metabolic effects of intravenous glucose infusion in human sepsis.

BACKGROUND: Sepsis is associated with alterations in glucose metabolism and the effect of intravenous feeding on energy expenditure is unclear. Many studies of glucose metabolism in humans with sepsis have employed techniques that are not relevant to the practice of intravenous feeding. METHODS: The thermogenic, hormonal and metabolic effects of glucose were evaluated in a prospective experimental study of septic (n = 6) and non-septic (n = 6) subjects, by administering glucose intravenously under conditions and at a rate similar to those used in total parenteral nutrition. RESULTS: Patients with sepsis had a higher fasting metabolic rate than control subjects (P < 0.001) and a lower fasting respiratory quotient (P < 0.03). The thermic effect of glucose in both groups was small and not statistically significant (median 3.2 and 0.4 per cent in septic and non-septic subjects respectively, P > 0.1). Patients with sepsis had an attenuated plasma insulin response to glucose administration compared with control subjects (P < 0.001) and less marked suppression of plasma fatty acid and glycerol concentrations (P < 0.001). Glucose administration was not associated with significant changes in plasma catecholamine concentrations in either group of patients. CONCLUSION: Intravenous infusion of glucose at clinically relevant rates is associated with a negligible thermogenic response, with no activation of the sympathetic nervous system.

Adult↗

PubMed1996

Tonsillar tissue penetration of dirithromycin after multiple doses.

Dirithromycin is a new macrolide antibiotic that is effective against group A beta-hemolytic streptococcal pharyngotonsillitis. This prospective, multicenter, randomized study compared the serum and tonsil tissue concentrations of erythromycylamine (to which dirithromycin is rapidly converted by nonenzymatic hydrolysis during absorption) and erythromycin after 5- and 10-day regimens of dirithromycin and erythromycin, respectively. Thirty-nine patients undergoing elective tonsillectomy but without active tonsillitis were assigned in randomized fashion to receive dirithromycin 500 mg orally once daily (n = 22) or erythromycin base 250 mg orally four times daily (n = 17). Data from 12 patients receiving dirithromycin and 10 receiving erythromycin were eligible for analysis. Mean serum concentrations (+/-standard deviation) of erythromycylamine and erythromycin were 0.20 +/- 0.07 microgram/mL and 0.12 +/- 0.25 microgram/mL, respectively, after the 5-day regimen and 0.17 +/- 0.10 microgram/mL and 1.57 +/- 3.16 micrograms/mL, respectively, after the 10-day regimen. The mean serum concentration of erythromycin after 10 days was skewed by the data for one of the six patients in the group (concentration of > 8 micrograms/mL). Mean concentrations of erythromycylamine in tonsil tissue were 4.62 +/- 0.97 micrograms/ g after 5 days and 3.47 +/- 2.84 micrograms/g after 10 days. Concentrations in tonsillar tissue were undetectable in all patients given erythromycin for 5 days and in 4 of the 6 patients given erythromycin for 10 days. The high concentrations of erythromycylamine in tonsillar tissue agree with the clinical efficacy seen in the treatment of group A beta-hemolytic streptococcal tonsillopharyngitis with dirithromycin.

Adolescent↗

PubMed1996

Dynamics and equilibrium behavior of cytonuclear disequilibria under genetic drift, mutation, and migration.

A simple two-locus drift model for cytonuclear systems is developed, in which the stochastic dynamics of cytonuclear genotypic frequencies are specified. Random union of zygotes is assumed. Trajectories for the first two moments of both genotypic and allelic disequilibria are given under three scenarios: (i) random drift alone; (ii) random drift with mutation; and (iii) random drift with migration. Steady state solutions for the cytonuclear disequilibria are reported. The utility of this simple two-locus drift model in testing the neutrality of mitochondrial DNA markers in artificial hybrid zones is briefly illustrated

DNA, Mitochondrial↗

PubMed1996

Endosome-lysosomes, ubiquitin and neurodegeneration.

Before the advent of ubiquitin immunochemistry and immunogold electron microscopy, there was no known intracellular molecular commonality between neurodegenerative diseases. The application of antibodies which primarily detect ubiquitin protein conjugates has shown that all of the human and animal idiopathic and transmissible chronic neurodegenerative diseases, (including Alzheimer's disease (AD), Lewy body disease (LBD), amyotrophic lateral sclerosis (ALS), Creutzfeldt-Jakob disease (CJD) and scrapie) are related by some form of intraneuronal inclusion which contains ubiquitin protein conjugates. In addition, disorders such as Alzheimer's disease, CJD and sheep scrapie, are characterised by deposits of amyloid, arising through incomplete breakdown of membrane proteins which may be associated with cytoskeletal reorganisation. Although our knowledge about these diseases is increasing, they remain largely untreatable. Recently, attention has focused on the mechanisms of production of different types of amyloid and the likely involvement within cells of the endosome-lysosome system, organelles which are immuno-positive for ubiquitin protein conjugates. These organelles may be 'bioreactor' sites for the unfolding and partial degradation of membrane proteins to generate the amyloid materials or their precursors which subsequently become expelled from the cell, or are released from dead cells, and accumulate as pathological entities. Such common features of the disease processes give new direction to therapeutic intervention.

Animals↗

PubMed1996

The validation of a 7-locus multiplex STR test for use in forensic casework. (I). Mixtures, ageing, degradation and species studies.

We have evaluated a multiplex STR system for routine forensic use, which co-amplifies six short tandem repeat (STR) loci; HUMTH01, D21S11, D18S51, D8S1179, HUMVWF31/A and HUMFIBRA (FGA), in conjunction with the X-Y homologous gene Amelogenin. Analysis of PCR products employs denaturing polyacrylamide gels coupled with fluorescent labelled primers and detection is undertaken on ABD 373A automated sequencers. The technique was shown to be robust and reproducible when samples were analysed under conditions consistent with those encountered in a forensic environment. The system was demonstrated to be human specific and is suitable for use with both aged and degraded material. Somatic stability was proven with a wide range of tissue types and we were able to detect mixtures at ratios between 1:10 and 10:1. During this study no incidence of sample mis-typing due to allelic or locus drop-out was observed. Furthermore, although additional artefact bands were occasionally encountered these did not interfere with the interpretation of results. The performance of the system with poor quality samples demonstrated its suitability as a powerful tool in forensic investigation.

Adult↗

PubMed1996

Indocyanine green angiographic features of pathologic myopia.

PURPOSE: To analyze indocyanine green angiographic findings of pathologic myopia and compare them with those of fluorescein angiography, with particular reference to the usefulness of indocyanine green angiography in the management of neovascular complications. METHODS: Thirty-two consecutive patients (52 eyes) with pathologic myopia underwent a complete ophthalmologic examination including fluorescein and indocyanine green angiography. RESULTS: Retrobulbar arteries and veins were visualized solely on indocyanine green angiography in 33 (63%) of 52 eyes. Choroidal arteries appeared attenuated and reduced in number. In the area of staphyloma, choroidal veins were less numerous, and in all eyes an absence of the normal choroidal flush caused by the choriocapillaris filling was observed. Subretinal and retinal hemorrhages were present in 28 (54%) of 52 eyes. Choroidal neovascularization was diagnosed in 16 eyes on fluorescein angiography and in 18 eyes on indocyanine green angiography. In seven eyes, indocyanine green angiography disclosed lacquer cracks (without choroidal neovascularization), appearing in the late phases as hypofluorescent lines, as the probable cause of the subretinal and retinal hemorrhages. In only one eye did indocyanine green angiography fail to disclose choroidal neovascularization detectable on fluorescein angiography. In two eyes, neither dye could clarify the origin of the hemorrhages. CONCLUSIONS: Indocyanine green angiography allows identification of retrobulbar arteries and veins, and analysis of the altered choroidal vasculature. Moreover, indocyanine green angiography is a useful diagnostic tool to differentiate lacquer cracks from choroidal neovascularization in retinal and subretinal hemorrhages.

Adolescent↗

PubMed1996

Exercise recordings for the detection of T wave alternans. Promises and pitfalls.

Despite significant advances in the treatment of sudden cardiac death, many individuals still go untreated because routine clinical tests do not identify them to be at risk. Recently, a study to identify individuals at risk has shown that the presence of T wave alternans (TWA), a fluctuation in T wave morphology occurring on an every-other-beat basis, is an accurate predictor of subsequent ventricular tachyarrhythmic events. T wave alternans as low as a few microvolts was found to be significant in predicting risk. Since TWA is often detectable only at elevated heart rates, the study used atrial pacing to increase the heart rate to approximately 100 beats/min. To make TWA measurement more broadly applicable, the authors have developed a methodology that uses noninvasive physiologic stress to raise the heart rate. A particular challenge was the measurement of TWA during exercise, since the levels of noise during exercise can far exceed the levels of TWA. However, by using special multisegment Hi-Res electrodes (Cambridge Heart, Bedford, MA), noise reduction software, and a spectral method of alternans analysis, the authors have been able to reduce noise and reliably measure microvolt-level alternans. This study presents an overview of the methodology for recording and analyzing microvolt-level TWA during ergometer exercise.

Adolescent↗

PubMed1996

Parallel computing of physical maps--a comparative study in SIMD and MIMD parallelism.

Ordering clones from a genomic library into physical maps of whole chromosomes presents a central computational problem in genetics. Chromosome reconstruction via clone ordering is usually isomorphic to the NP-complete Optimal Linear Arrangement problem. Parallel SIMD and MIMD algorithms for simulated annealing based on Markov chain distribution are proposed and applied to the problem of chromosome reconstruction via clone ordering. Perturbation methods and problem-specific annealing heuristics are proposed and described. The SIMD algorithms are implemented on a 2048 processor MasPar MP-2 system which is an SIMD 2-D toroidal mesh architecture whereas the MIMD algorithms are implemented on an 8 processor Intel iPSC/860 which is an MIMD hypercube architecture. A comparative analysis of the various SIMD and MIMD algorithms is presented in which the convergence, speedup, and scalability characteristics of the various algorithms are analyzed and discussed. On a fine-grained, massively parallel SIMD architecture with a low synchronization overhead such as the MasPar MP-2, a parallel simulated annealing algorithm based on multiple periodically interacting searches performs the best. For a coarse-grained MIMD architecture with high synchronization overhead such as the Intel iPSC/860, a parallel simulated annealing algorithm based on multiple independent searches yields the best results. In either case, distribution of clonal data across multiple processors is shown to exacerbate the tendency of the parallel simulated annealing algorithm to get trapped in a local optimum.

Algorithms↗

PubMed1996

PARODS--a study of parallel algorithms for ordering DNA sequences.

A suite of parallel algorithms for ordering DNA sequences (termed PARODS) is presented. The algorithms in PARODS are based on an earlier serial algorithm, ODS, which is a physical mapping algorithm based on simulated annealing. Parallel algorithms for simulated annealing based on Markov chain decomposition are proposed and applied to the problem of physical mapping. Perturbation methods and problem-specific annealing heuristics are proposed and described. Implementations of parallel Single Instruction Multiple Data (SIMD) algorithms on a 2048 processor MasPar MP-2 system and implementations of parallel Multiple Instruction Multiple Data (MIMD) algorithms on an 8 processor Intel iPSC/860 system are presented. The convergence, speedup and scalability characteristics of the aforementioned algorithms are analyzed and discussed. The best SIMD algorithm is shown to have a speedup of approximately 1000 on the 2048 processor MasPar MP-2 system, whereas the best MIMD algorithm is shown to have a speedup of approximately 5 on the 8 processor Intel iPSC/860 system.

Algorithms↗

PubMed1996

On the consistency of a physical mapping method to reconstruct a chromosome in vitro.

During recent years considerable effort has been invested in creating physical maps for a variety of organisms as part of the Human Genome Project and in creating various methods for physical mapping. The statistical consistency of a physical mapping method to reconstruct a chromosome, however, has not been investigated. In this paper, we first establish that a model of physical mapping by binary fingerprinting of DNA fragments is identifiable using the key assumption-for a large randomly generated recombinant DNA library, there exists a staircase of DNA fragments across the chromosomal region of interest. Then we briefly introduce epi-convergence theory of variational analysis and transform the physical mapping problem into a constrained stochastic optimization problem. By doing so, we prove epi-convergence of the physical mapping model and epi-convergence of the physical mapping method. Combining the identifiability of our physical mapping model and the epi-convergence of a physical mapping method, finally we establish strong consistency of a physical mapping method.

Aspergillus nidulans↗