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Biomedical subjects

J Harrington

Publications and source records attributed to J Harrington.

At least 37 records · Page 2Linked to original sources
PubMed1995

Lagging strand DNA synthesis at the eukaryotic replication fork involves binding and stimulation of FEN-1 by proliferating cell nuclear antigen.

The 5'-->3'-exonuclease domain of Escherichia coli DNA polymerase I is required for the completion of lagging strand DNA synthesis, and yet this domain is not present in any of the eukaryotic DNA polymerases. Recently, the gene encoding the functional and evolutionary equivalent of this 5'-->3'-exonuclease domain has been identified. It is called FEN-1 in mouse and human cells and RTH1 in Saccharomyces cerevisiae. This 42-kDa enzyme is required for Okazaki fragment processing. Here we report that FEN-1 physically interacts with proliferating cell nuclear antigen (PCNA), the processivity factor for DNA polymerases delta and epsilon. Through protein-protein interactions, PCNA focuses FEN-1 on branched DNA substrates (flap structures) and on nicked DNA substrates, thereby stimulating its activity 10-50-fold but only if PCNA can functionally assemble as a toroidal trimer around the DNA. This interaction is important in the physical orchestration of lagging strand synthesis and may have implications for how PCNA stimulates other members of the FEN-1 nuclease family in a broad range of DNA metabolic transactions.

Base Sequence↗
PubMed1995

Healthcare Information Framework.

CEN committee TC 251 Medical Informatics, has set up a project team charged with producing a European pre-standard ENV on Healthcare Information Framework (HIF). The HIF is based on abstraction from a specific information system architecture to a reference architecture and further to a conceptual architectural framework based on serving open, distributed and heterogeneous healthcare enterprises. To specify the suitable healthcare information system architecture modelling of the healthcare enterprise is required. As there is no one method serving all needs, the HIF gives guidance on what aspects to look at in selecting a suitable modelling method. It is expected that the work will be completed by early 1995.

Artificial Intelligence↗
PubMed1995

In vitro growth of neonatal rat islet cells is stimulated by adhesion to matrix.

We examined DNA synthesis in non-enzymatically isolated neonatal rat pancreatic islets sub-cultured to eliminate fibroblast contamination, which was excluded both by demonstrating no effect of fibroblast growth factor (FGF) on 3H-thymidine incorporation and by immunofluorescence of attached islets using a mouse anti-fibroblast monoclonal antibody. 3H-thymidine incorporation in islets increased with increasing glucose up to a concentration of 21.1 mM in both free-floating islets (11,789 cpm/micrograms DNA +/- 1,610 SEM) and islets attached to fibronectin coated plastic (43,043 cpm/micrograms DNA +/- 9,203 SEM). These values were significantly higher when compared to 3H-thymidine incorporation in medium containing 11.1 mM glucose (p < 0.007, and p < 0.0001 for free-floating and attached islets respectively). 3H-thymidine incorporation was significantly higher in attached islets than in free-floating islets at all glucose concentrations tested (p < 0.005 at 11.1 mM, 16.1 mM, and 21.1 mM; and p < 0.01 at 26.1 mM). 5-bromo-2'-deoxyuridine (BrDU) staining of islets showed an increased number of positive nuclei in cells localised within attached islets (37.6 nuclei per islet +/- 5.1 SEM) compared to free-floating islets (7.62 nuclei per islet +/- 1.04 SEM, p < 0.001), indicating that attachment influenced proliferation of islet cells not physically in contact with the matrix. No difference in glucose-stimulated insulin release was observed between attached and free-floating islets. In conclusion, a fibroblast free islet culture was used to document the stimulatory effect of islet attachment on DNA synthesis, which was greater than the stimulation exerted by glucose alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Insulin secretion and DNA synthesis of cultured islets of Langerhans are influenced by the matrix.

To compare the effect of matrix on glucose-stimulated insulin release, we cultured neonatal (3- to 5-day-old) rat islets of Langerhans, devoid of mesenchymal cell, on fibronectin, Cell-Tak, or endothelial basement membranes, free-floating, or dispersed into single cells. We also examined the rate of DNA synthesis during the culture period. Compared to free-floating islets [0.386 +/- 0.03 (SEM) ng per 24 h/ng total], single-cell cultures had the lowest basal insulin release (0.159 +/- 0.03 ng per 24 h/ng total; p < 0.0001), which was also low in islets attached to endothelial basement membrane (0.294 +/- 0.02 ng per 24 h/ng total; p = 0.01). The spontaneous insulin release (1 h in medium with 2.7 mM glucose) was lowest in islets attached to endothelial basement membrane (0.003 +/- 0.00023 ng per h/ng total; p < 0.0001 vs. free-floating) and highest in single-cell cultures (0.01153 +/- 0.00259 ng per h/ng total; p = 0.039 vs. free-floating). The ability to increase insulin release following a glucose challenge (16.1 mM for 1 h) was highest in islets grown on endothelial basement membranes (16.4-fold) and fibronectin (12.6-fold) compared to free-floating islets (8.7-fold), Cell-Tak (7.9-fold), and single-cell cultures (5.4-fold).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Asthma severity and morbidity in a population sample of Sydney school children: Part I--Prevalence and effect of air pollutants in coastal regions.

BACKGROUND: In two regions of Sydney where sewage treatment facilities with high temperature sludge burning incinerators are installed, there was concern that the resultant emissions were causing a local increase in symptoms of asthma and other allergic diseases. AIM: To investigate whether living in a region with high temperature sludge burning incinerators was associated with an increased prevalence of childhood asthma or allergy. METHODS: We studied 713 children aged eight-12 years in two regions close to incinerators and 626 children in a control region with no sludge burning incinerator. We measured respiratory illness in the previous year by questionnaire, airway hyper-responsiveness (AHR) by histamine inhalation test, and atopy by skin prick tests. 'Current asthma' was defined as AHR and recent wheeze. RESULTS: Recordings of oxides of nitrogen and sulphur, hydrogen sulphide, ozone and particulates during the study period showed that the level of pollutants did not vary in any major way between the study regions and the control region. The prevalence of current asthma, atopy, symptom frequency or any category of severity of asthma illness was not significantly different between the control and study regions. CONCLUSIONS: This suggests that factors other than intermittent or industrial air pollutants are responsible for the high prevalence of asthma symptoms, asthma medication use, asthma morbidity and AHR in the study of children.

Air Pollutants↗
PubMed1994

The contribution of the murmur and vowel to the place of articulation distinction in nasal consonants.

Recent studies have shown that the acoustic relationship between the murmur and the vowel at the nasal-vowel boundary is highly informative for the [m]-[n] distinction. In the present paper, the contribution of relational information is reassessed by classifying 1946 syllable-initial and 2848 syllable-final nasal consonants taken from continuous speech data. Relational information in the acoustic waveform is based on difference spectra, in which spectral information in the vowel is subtracted from spectral information in the murmur, and on combined spectra in which classifications are made from combinations of murmur and vowel spectra. These two kinds of relational spectra are compared with static spectra, in which single spectral slices are taken in either the murmur or the vowel. Contrary to recent theoretical predictions, difference spectra are shown to perform more poorly than some kinds of static spectra. However, since classification scores from combined spectra are better than from either static or difference spectra, cues to nasal place of articulation can nevertheless be defined as relational. In the best scoring combined spectra, classification scores on open tests are just under 94% correct for syllable-initial nasals and just under 82% correct for syllable-final nasals. The high classification scores show that there is considerable information in the acoustic waveform for identifying nasal place of articulation from continuous speech data.

Female↗
PubMed1993

Recommendations for an object oriented healthcare information model.

The need for a healthcare information model as a component in a framework of standards for healthcare data interchange is identified. Key requirements for a method to support development of a healthcare information model are defined and recommendations for development of an Object Oriented Healthcare Information Model are presented.

Computer Communication Networks↗
PubMed1992

Analysis of the defect in DNA end joining in the murine scid mutation.

Murine severe combined immune deficiency (scid) is marked by a 5,000-fold reduction in coding joint formation in V(D)J recombination of antigen receptors. Others have demonstrated a sensitivity to double-strand breaks generated by ionizing radiation and bleomycin. We were interested in establishing the extent of the defect in intramolecular and intermolecular DNA end joining in lymphoid and nonlymphoid cells from scid mice. We conducted a series of studies probing the ability of these cells to resolve free ends of linear DNA molecules having various biochemical end configurations. We find that the stable integration of linear DNA into scid fibroblasts is reduced 11- to 75-fold compared with that in normal fibroblasts. In contrast, intramolecular and intermolecular end joining occur at normal frequencies in scid lymphocytes and fibroblasts. This normal level of end joining is observed regardless of the type of overhang and regardless of the requirement for nucleolytic activities prior to ligation. The fact that free ends having a wide variety of end configurations are recircularized normally in scid cells rules out certain models for the defect in scid. We discuss the types of DNA end joining reactions that are and are not affected in this double-strand break repair defect in the context of a hairpin model for V(D)J recombination.

Animals↗
PubMed1991

Differences in cerebral blood flow between alpha-stat and pH-stat management are eliminated during periods of decreased systemic flow and pressure. A study during cardiopulmonary bypass in rabbits.

Prior reports suggest cerebral blood flow (CBF) responses to changing bypass (systemic) flow rates may differ between alpha-stat and pH-stat management. To compare the effect of blood gas management upon CBF responses to changing systemic flow and pressure, 15 New Zealand White rabbits, anesthetized with fentanyl and diazepam, underwent nonpulsatile cardiopulmonary bypass at 25 degrees C. One group of animals (n = 8) was randomized to alpha-stat blood gas management that maintained arterial carbon dioxide tension (PaCO2) approximately 40 mmHg when measured at 37 degrees C. A second group (n = 7) was managed with pH-stat technique, maintaining PaCO2 approximately 40 mmHg when corrected to the animal's actual temperature. Bypass was initiated at a flow rate of 100 ml.kg-1.min-1 and, after approximately 20 min, control hemodynamic and CBF measurements (radioactive microspheres) were made. Thereafter, bypass flow rate was changed in random order at 15-min intervals to 50, 70, and 100 ml.kg-1.min-1. CBF and hemodynamic measurements were repeated at the end of each period of altered bypass flow. Groups differed significantly with respect to both pHa and PaCO2. There were no significant differences between groups with respect to bypass flow rate, mean arterial pressure (MAP), central venous pressure, temperature, hematocrit, arterial oxygen tension (PaCO2), or bypass duration at any measurement point. MAP decreased significantly, from approximately 80 to approximately 65 mmHg with decreasing bypass flow (P = 0.0001). Over the entire range of bypass flows, CBF decreased with decreasing bypass flow (P = 0.001), and the degree of change was equivalent among regions and between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Cerebral blood flow response to PaCO2 during hypothermic cardiopulmonary bypass in rabbits.

Differences in cerebral blood flow (CBF) between alpha-stat and pH-stat management depend on preserved responsiveness of the cerebral vasculature to changes in arterial carbon dioxide tension (PaCO2). We tested the hypothesis that hypothermia-induced reductions in CBF would decrease the CBF response to changing PaCO2 (delta CBF/delta PaCO2). Anesthetized New Zealand white rabbits were randomly assigned to one of three temperature groups--group 1 (37 degrees C, n = 9); group 2 (31 degrees C, n = 10); or group 3 (25 degrees C, n = 10)--and were cooled using cardiopulmonary bypass. After esophageal temperature equilibration (approximately 40 min), oxygenator gas flows were serially varied to achieve PaCO2 values of 20, 40, and 60 mm Hg (temperature-corrected). All animals were studied at all three PaCO2 levels in random order. At each level of PaCO2, CBF and masseter blood flow were determined using radiolabeled microspheres. There were no significant differences between groups with respect to mean arterial pressure (approximately 80 mmHg), central venous pressure (approximately 4 mmHg), or hematocrit (approximately 22%). Prior normothermic studies have found delta CBF/delta PaCO2 to be proportional to CBF. Nevertheless, in this study, with hypothermia-induced reductions in CBF, delta CBF/delta PaCO2 was not significantly different between temperature groups. Thus, hypothermia either increased the sensitivity of the cerebral vasculature to carbon dioxide and/or increased the effective level of cerebrospinal fluid respiratory acidosis produced by each increment of temperature-corrected PaCO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Haptoglobin typing in canine bloods.

Haptoglobin typing by vertical electrophoresis in a discontinuous polyacrylamide gel was conducted on 47 dog blood samples, of which 19 were from Doberman pinschers, 20 from German shepherds, and 8 from pit bullterriers. Two phenotypes were common in the three breeds and could not be used to differentiate between them. Canine haptoglobin phenotypes were, however, sufficiently different from those of humans to warrant using haptoglobin typing as a method for determining the origin of bloodstains.

Animals↗
PubMed1990

The networking standards evolution: toward a real electronic medical record. Interview by Carolyn Dunbar.

While converging networking standards have created short- and long-term options for healthcare IS planners, one strong goal is a "life-long, longitudinal electronic medical record" that includes data of all types--text, wave forms, voice, images and other pictorial data. Jack Harrington of Hewlett-Packard says these complex efforts are shaped by major forces that now speed progress toward multilateral acceptance of a uniform standard.

Computer Communication Networks↗
PubMed1989

Cyclic AMP-dependent melatonin production in Y79 human retinoblastoma cells.

Melatonin is rhythmically synthesized in some vertebrate retinas and has been implicated in the regulation of key rhythmic events in the photoreceptor-pigment epithelial complex. In human retina, melatonin is present; however, no information exists on the cellular regulation of this hormone. We report here that the established human retinoblastoma cell line Y79 synthesizes and releases melatonin. Treatments that elevate cyclic AMP (cAMP) levels (forskolin, 8-Br-cAMP, and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine) all stimulate melatonin release from static cultures of Y79 cells. Other 8-bromo nucleotide analogues (cyclic GMP, ATP, and AMP) are not effective. These results suggest that Y79 human retinoblastoma cells require a cAMP-dependent mechanism for melatonin biosynthesis similar to that described previously in other vertebrates. This is the first demonstration of melatonin release from a cultured human cell line. These results support the idea that human retinal cells share homologies with pineal cells, as suggested by the condition trilateral retinoblastoma.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Stuttering, delayed auditory feedback, and linguistic rhythm.

The models of stuttering and delayed auditory feedback (DAF) discussed in this paper are derived from a model of the fluent production of speech in which a rhythmic structure prespecifies the intervals between vowels of stressed syllables. The same rhythmic structure enables a prediction to be made concerning when vowels of stressed syllables will be auditorily perceived. In both stuttering and speech produced under DAF conditions, it is suggested that an incorrect prediction is made concerning when the vowel will be perceived relative to its production. The proposed model of stuttering can account for a variety of other phenomena. Finally, a preliminary model of the onset of stuttering in children is proposed.

Auditory Perception↗