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Biomedical subjects

J Arnold

Publications and source records attributed to J Arnold.

At least 19 recordsLinked to original sources
PubMed1992

The application of Markov chain analysis to oligonucleotide frequency prediction and physical mapping of Drosophila melanogaster.

Here we compare several methods for predicting oligonucleotide frequencies in 691 kb of Drosophila melanogaster DNA. As in previous work on Escherichia coli and Saccharomyces cerevisiae, a relatively simple equation based on tetranucleotide frequencies can be used in predicting frequencies of higher order oligonucleotides. For example, the mean of observed/expected abundances of 4,096 hexamers was 1.07 with a sample standard deviation of .55. This simple predictor arises by considering each base on the sense strand of D. melanogaster to depend only on the three bases 5' to it (a 3rd order Markov chain) and is more accurate than the random predictor. This equation is useful in predicting restriction enzyme fragment sizes, selecting restriction enzymes that cut preferentially in coding vs noncoding regions, and in selecting probes to fingerprint clones in contig mapping. Once again, this equation well predicts the occurrence of higher order oligonucleotides, supporting our hypothesis that this predictor holds in evolutionarily diverse organisms. When ranked from highest to lowest abundance, the observed frequencies of oligomers of a given length are closely tracked by the predicted abundances of a 3rd order Markov chain. Through use of the dependence of oligomer frequencies on base composition, we report a list of oligomers that will be useful for the completion of a cosmid physical map of D. melanogaster. Presently, the library is such that it will be possible to construct large contigs using only 30 oligonucleotide probes to fingerprint cosmids.

Animals↗
PubMed1992

The role of interleukin 6 in megakaryocyte formation, megakaryocyte development and platelet production.

Megakaryocytopoiesis is the cellular amplification and differentiation of precursors into immature megakaryocytes, and the cytoplasmic maturation of these megakaryocytes, a process terminating in the release of platelets into the circulation. Interleukin 6 (IL-6) stimulates megakaryocytopoiesis in the bone marrow, increasing platelet numbers in the circulation. IL-6 alone is poorly active on the growth of stem cell populations, but acts in synergy with stem cell factor (c-kit ligand) to expand the committed myeloid progenitor compartments but not the megakaryocyte progenitors. IL-6 has a direct action on megakaryocyte progenitors but only in synergy with low doses of interleukin 3 (IL-3), increasing the number of immature megakaryocytes and enhancing the processes of development into mature megakaryocytes. IL-6 is about 10 times more active on megakaryocytes than on megakaryocyte progenitors in cell culture. It is active alone and will stimulate increases in cell size and DNA content. IL-6 does not appear to stimulate the process of platelet release. IL-6 is found in bone marrow, in both macrophage subsets and megakaryocytes, indicating that it may be an important physiological regulator of both paracrinal (microenvironmental) and autocrinal mechanisms controlling megakaryocyte development in bone marrow.

Animals↗
PubMed1992

Follow-up of patients with hepatitis non-A, non-B: incidence and persistence of anti-HCV depend on route of transmission.

Of 32 patients with non-A, non-B hepatitis, 10 (31%) were still anti-HCV-positive 12.8 years after the acute phase of the disease. Seven of the patients (21.9%) still had elevated ALT levels, and among these, 5 out of 5 patients who had been subject to parenteral risk were anti-HCV-positive. In contrast, none of the patients who had not been subject to parenteral risks were positive.

Follow-Up Studies↗
PubMed1992

Dynamics of cytonuclear disequilibria in finite populations and comparison with a two-locus nuclear system.

We study the behavior of cytonuclear disequilibria in a finite monoecious population due to (1) random drift alone, (2) random drift and mutation, and (3) random drift and migration, using exact results on the RUZ (Random Union of Zygotes) model and diffusion approximations. We also show that the RUG (Random Union of Gametes) model is not suitable for a cytonuclear system. The study is also accompanied by a comparison with a two-locus nuclear system. We show that in a finite population of size N without mutation, the rate of decrease of the cytonuclear allelic disequilibrium is the same as that in the corresponding unlinked two-locus nuclear system. The principal rate of decrease of variance in allelic disequilibrium in a cytonuclear system is slightly faster than that in the corresponding nuclear system. However, the expected value of the variance in cytonuclear disequilibria is larger than that in a two-locus nuclear system for at least the first N generations. With mutation, the expected value of steady state variances of both systems are about the same; however, the normalized variance in linkage disequilibrium sigma 2d of the cytonuclear system is about twice as large as that for the corresponding nuclear system. For the migration process, two sets of steady state solutions are provided, one for the variables before migration and the other for the variables after migration. Diffusion approximations for both the principal rate of decay and steady state solutions in both systems are found to be satisfactory. A more accurate backward diffusion equation for a two-locus nuclear system is provided when the recombination fraction R is large.

Animals↗
PubMed1992

CMAP: contig mapping and analysis package, a relational database for chromosome reconstruction.

In the contig mapping and analysis package, CMAP, we provide a foundation for reverse genetics by organizing information about DNA fragments obtained from an organism's genome into a physical map. The user can store information about a particular segment of DNA. This information can be both descriptive, such as any genes contained in a particular DNA fragment, or experimental, such as hybridization profiles or restriction digest patterns for comparison with other fragments. The package can then be instructed to update the physical map or provide information on a DNA fragment within the map, such as its location. The user interface is designed to minimize the learning curve associated with database usage, while eliminating the possibility of entering data outside the ranges of fields through error-checking protocols. Queries are currently accomplished by the use of dynamic SQL (structured query language), which gives the user the ability to build queries based on any combination of the attributes contained within the database without requiring that all possible queries be permanently programmed within the query software. In order to eliminate the need for knowledge of SQL, an interface was designed to allow users to build queries by menu choices. Thus, CMAP is a software package supporting a database for both the production and storage of a physical map as well as being the first step toward the production of a physical mapping workstation.

Algorithms↗
PubMed1992

The use of simulated annealing in chromosome reconstruction experiments based on binary scoring.

We present a method of combinatorial optimization, simulated annealing, to order clones in a library with respect to their position along a chromosome. This ordering method relies on scoring each clone for the presence or absence of specific target sequences, thereby assigning a digital signature to each clone. Specifically, we consider the hybridization of oligonucleotide probes to a clone to constitute the signature. In that the degree of clonal overlap is reflected in the similarity of their signatures, it is possible to construct maps based on the minimization of the differences in signatures across a reconstructed chromosome. Our simulations show that with as few as 30 probes and a clonal density of 4.5 genome equivalents, it is possible to assemble a small eukaryotic chromosome into 33 contiguous blocks of clones (contigs). With higher clonal densities and more probes, this number can be reduced to less than 5 contigs per chromosome.

Algorithms↗
PubMed1992

Positional asphyxia during law enforcement transport.

Three cases of positional asphyxia are described that occurred while victims were in a prone position in rear compartments of police patrol cars. These deaths are attributed to positional asphyxia. Autopsy findings and specific scene and circumstantial correlations of the investigation are discussed with emphasis placed on the limitations of interpretation of the anatomic changes at autopsy.

Adult↗
PubMed1992

A comparison of upper gastrointestinal mucosal damage by standard and delayed-release indomethacin.

Forty-five patients taking long-term indomethacin and with endoscopic erosions or superficial ulcers in the oesophagus, stomach or duodenal bulb were randomized in a double-blind study to continue with standard indomethacin or receive a 'delayed-release' formulation. This consisted of microgranules of indomethacin coated with an acrylic resin, Eudragit L, which releases drug in the small intestine. Endoscopy was repeated after 8 weeks and biopsies taken on both occasions. Changes in endoscopic lesions and histological appearances were similar in both groups, although mucosal erythema was less in those given Eudragit L indomethacin. Systemic, rather than topical, effects of indomethacin may therefore be responsible for persistence of gastro-duodenal mucosal lesions in these patients. There is reason to question the clinical practice of using expensive, delayed-release preparations.

Adult↗
PubMed1992

Time course of some effects of cigarette smoking on platelets.

Eight male habitual smokers smoked two cigarettes over a 20-min period following a 12-h period of abstinence. Antecubital venipuncture was performed immediately before, immediately after, and 55 min and 2 h after smoking had ceased. At these times, the mean values (+/- SD) of collagen-induced platelet aggregation were 45 +/- 5, 68 +/- 5, 59 +/- 6 and 52 +/- 5 chart units, respectively, while the corresponding values for the mean platelet aggregate ratio were 0.91 +/- 0.01, 0.82 +/- 0.03, 0.87 +/- 0.02 and 0.90 +/- 0.02, respectively. Mean collagen-induced platelet aggregation was significantly (P less than 0.005) higher immediately after, and 55 min and 2 h after smoking. The mean platelet aggregate ratio was significantly (P less than 0.001) lower immediately after and 55 min after smoking. Correlation coefficients between the concentration of nicotine in each of the 24 plasma samples obtained after smoking and the corresponding values of collagen-induced platelet aggregation and the platelet aggregate ratio were 0.41 (P less than 0.05) and -0.50 (P less than 0.02), respectively. It is concluded that when habitual smokers abstain from smoking overnight, a 20-min period of cigarette smoking may enhance platelet aggregability for as long as 2 h.

Adult↗
PubMed1992

Thermogenic and hormonal responses to amino acid infusion in septic humans.

Metabolic effects of a commercially available amino acid infusate were investigated in five preoperative patients with abdominal sepsis and five healthy subjects. Oxygen consumption (VO2) was measured continuously during the 3-h study, and blood samples were taken regularly for hormone and metabolite analyses. During 1 h of preinfusion measurements, VO2 was 15% higher (P less than 0.05) in the septic patients. Preinfusion plasma cortisol, glucagon, and catecholamines were also significantly elevated in the septic group. The amino acid solution (9 g nitrogen; 950 kJ; 227 kcal) was infused into each subject through their central venous catheter during the 2nd and 3rd h of the study. VO2 increased similarly in both groups by approximately 21% during the infusion (P less than 0.05), whereas respiratory quotient increased significantly in only the controls (P less than 0.05). Plasma insulin and glucagon concentrations rose significantly in both groups during the infusion, despite little change in glucose levels. Plasma norepinephrine increased in both groups, although the response was significant in only the control subjects. In summary, the amino acid infusate stimulated metabolic rate similarly in the septic and nonseptic subjects.

Amino Acids↗
PubMed1992

Risk of ulceration with long-term indomethacin: endoscopic and histological changes in upper gastro-intestinal mucosa.

Twenty patients taking long-term indomethacin were chosen for the study because all had a normal endoscopic examination; biopsies, however, from the oesophagus, gastric antrum and duodenal bulb revealed histological inflammation in all patients in at least one site. After 8 weeks during which indomethacin therapy was continued, a further endoscopy revealed lesions in 5 patients--peptic ulcer in 3 and erosions in 2--but only 1 of these had any change in gastro-intestinal symptoms. Irrespective of whether mucosal lesions are seen on endoscopy in patients established on non-steroidal anti-inflammatory drug therapy, they remain in danger of developing both ulcers and erosions which are likely to be asymptomatic. At no time can one justifiably feel this patient group is not at risk of peptic ulceration.

Arthritis, Rheumatoid↗
PubMed1992

[Liver transplantation after trans-jugular intrahepatic portosystemic stent shunt].

Every third patient with parenchymal liver disease bleeds from esophageal varices. Treatment of this complication is of special interest with regard to liver transplantation which may become necessary later on. The mesocaval H-shunt excluded, surgical shunting results in technical and hemodynamic problems during transplantation. They may be avoided by the new approach of transjugular intrahepatic portosystemic stent shunt (TIPSS). We report our experience with liver transplantation in two patients after TIPSS.

Adult↗
PubMed1992

Combination biotherapy utilizing interleukin-2 and alpha interferon in patients with advanced cancer: a National Biotherapy Study Group Trial.

The National Biotherapy Study Group (NBSG) conducted a broad phase II trial using interleukin-2 (IL-2) by continuous infusion and alpha interferon (IFN) subcutaneously in 267 patients with a variety of advanced cancers, including 29 with breast cancer, 89 with renal cancer, and 69 with melanoma. IL-2 [18 million international units (MIU)/m2] was given by continuous infusion for 108 hours with 3 mu/m2 subcutaneous IFN every other day during the IL-2 infusion. The patients were treated for 1 week followed by a 2-week rest. After two cycles of treatment, patients were evaluated for response. Of the 237 patients evaluable for response, 20 (8%) had a complete or partial response and 128 (54%) were stable. Therefore, 62% of the evaluable patients were nonprogressive during the first 90 days of IL-2/IFN therapy. The objective response rate was 11% in melanoma, 7% in renal cancer, 14% in breast cancer, and 3% in patients with a variety of malignancies for an overall response rate of 7% in these patients with advanced cancer. The patients were treated on a general medical ward and tolerated treatment well with fatigue and fever being nearly universal. Dyspnea, pruritus, chills, and elevated creatinines were frequent but less common. This combination biotherapy regimen has minimal activity in a variety of advanced cancers and must be compared with the best existing chemotherapy for each cancer type in randomized, prospective trials.

Adult↗
PubMed1992

On the design of genome mapping experiments using short synthetic oligonucleotides.

The DNA of an organism can be digested into smaller fragments, stored individually as clones in phage, for example, to create a clone library, and retrieved later, when needed. The original ordering of fragments is lost in the process of creating the library. Hence, it is important to be able to place clones in order according to their position along chromosome(s), and this process is referred to as "in vitro reconstruction" or "contig mapping" of an organismal genome. Clones in the phage library can be assigned binary call numbers by scoring each clone for hybridization (0 or 1) with a battery of short manufactured DNA sequences called synthetic oligonucleotides or with restriction enzyme digests of each clone. Those clones with similar call numbers are placed close together in the ordered library. We address the design question of how many clones and probes to use to carry out in vitro reconstruction of an organism's chromosomes. This physical mapping problem is placed in the context of coverage problems in geometrical probability. Various statistics are developed to summarize how an ordered library covers a chromosome, the extent of clone overlap, and the similarity between clone call numbers. Several tests for whether clones overlap are given, together with their power properties. A simulation study is used to determine how robust some of the tests for clone overlap are to model violations. Tables are presented for researchers to choose the number of clones and probes on the basis of both power and technical considerations surrounding the hybridization experiments.

Animals↗