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Biomedical subjects

G Geiger

Publications and source records attributed to G Geiger.

At least 19 recordsLinked to original sources

Intracellular action of the cytokine MIF to modulate AP-1 activity and the cell cycle through Jab1.

Cytokines are multifunctional mediators that classically modulate immune activity by receptor-mediated pathways. Macrophage migration inhibitory factor (MIF) is a cytokine that has a critical role in several inflammatory conditions but that also has endocrine and enzymatic functions. The molecular targets of MIF action have so far remained unclear. Here we show that MIF specifically interacts with an intracellular protein, Jab1, which is a coactivator of AP-1 transcription that also promotes degradation of the cyclin-dependent kinase inhibitor p27Kip1 (ref. 10). MIF colocalizes with Jab1 in the cytosol, and both endogenous and exogenously added MIF following endocytosis bind Jab1. MIF inhibits Jab1- and stimulus-enhanced AP-1 activity, but does not interfere with the induction of the transcription factor NFkappaB. Jab1 activates c-Jun amino-terminal kinase (JNK) activity and enhances endogenous phospho-c-Jun levels, and MIF inhibits these effects. MIF also antagonizes Jab1-dependent cell-cycle regulation by increasing p27Kip1 expression through stabilization of p27Kip1 protein. Consequently, Jab1-mediated rescue of fibroblasts from growth arrest is blocked by MIF. Amino acids 50-65 and Cys 60 of MIF are important for Jab1 binding and modulation. We conclude that MIF may act broadly to negatively regulate Jab1-controlled pathways and that the MIF-Jab1 interaction may provide a molecular basis for key activities of MIF.

COP9 Signalosome Complex↗

Amplifiable DNA from gram-negative and gram-positive bacteria by a low strength pulsed electric field method.

An efficient electric field-based procedure for cell disruption and DNA isolation is described. Isoosmotic suspensions of Gram-negative and Gram-positive bacteria were treated with pulsed electric fields of <60 V/cm. Pulses had an exponential decay waveform with a time constant of 3.4 micros. DNA yield was linearly dependent on time or pulse number, with several thousand pulses needed. Electrochemical side-effects and electrophoresis were minimal. The lysates contained non-fragmented DNA which was readily amplifiable by PCR. As the method was not limited to samples of high specific resistance, it should be applicable to physiological fluids and be useful for genomic and DNA diagnostic applications.

Cell Fractionation↗

A quantitative fluorescence-based microplate assay for the determination of double-stranded DNA using SYBR Green I and a standard ultraviolet transilluminator gel imaging system.

Various assays are available for quantification of DNA in solution, but none has been described that is both sensitive and specific for double-stranded (ds) DNA and features practical properties such as low dye and equipment costs, speed, and highly parallel microplate formats. Here we show that quantitative and sensitive measurement of ds DNA in solution is achieved using a 96-well microplate SYBR Green I assay and a standard uv transillumination-based gel-imaging system for detection. Specific detection of ds DNA was obtained over a broad concentration range of 0.5-500 ng using a single low dye concentration of up to 1/6250. Measured SYBR Green I fluorescence was not significantly affected by pH variation (4-10), assay volume (50-250 microliter l), and time (4-15 min), and measurements were appreciably compatile with commonly encountered concentrations of contaminating salts, organics, detergents, and other substances. ds DNA yielded up to 13-fold higher fluorescence compared to single-stranded DNA or RNA, but this ratio was dependent somewhat on GC content and fragment size. Of note, linear ds DNA fluoresced significantly stronger than supercoiled plasmid DNA. Our method should be broadly applicable for sensitive, rapid, and inexpensive ds DNA quantification in the average molecular biology laboratory.

Base Composition↗

Heavy metal effects on beta-glucosidase activity influenced by pH and buffer systems.

Inhibition of beta-glucosidase activity by Cu(II), Zn(II) and Ni(II) was investigated as a function of pH and buffer type. Both factors were found to exert a strong effect on the activity of the enzyme. All three of the investigated heavy metals inhibited the enzyme activity in acetate buffer. At metal concentrations of 0.6 mM, Zn and Ni reduced the enzyme activity by 25-30% under optimal pH conditions (pH 5-5.2). Under the same conditions, Cu showed an even more pronounced inhibitory effect than Zn and Ni. In presence of 0.6 mM Cu, the enzyme activity was lowered by more than 90% in comparison to metal free systems. In contrast to these results, no enzyme inhibition was observed in citrate buffer, even in the presence of 1 mM Cu. The inhibition of beta-glucosidase activity by Cu increased with increasing pH. Inhibition by Zn and Ni was less pH-dependent in the observed pH range (pH 4-5.5). Copper caused a distinct shift in the pH optimum of enzyme activity, whereas this was not the case for Zn or Ni. The effects of buffer and pH on enzyme inhibition by Cu, Zn and Ni were successfully described using a chemical speciation model, based on the assumption that enzyme activity depends on the protonation of the amino acids at the reactive site and that enzyme activity is inhibited by complexation of the reactive sites by the heavy metal cations. The results show the importance of taking chemical conditions and speciation into account when investigating the effect of heavy metal cations on biological systems.

Buffers↗

Moving towards an electronic patient record: a survey to assess the needs of community family physicians.

OBJECTIVE: To determine the needs of community family physicians regarding electronic patient records (EPRs). DESIGN: A comprehensive survey was sent to 101 community family physicians in Hamilton, Ontario, who had expressed an interest in EPRs. RESULTS: 46 physicians responded (46%). 87% felt that an EPR would result in their providing better patient care. A wide variety of items were deemed to be important to be included on the EPR "front page". Desired functionality emphasized labs, medications, consultation, hospital follow-up and health maintenance. Family physicians tended to prefer templates to other data entry methods such as typing and dictating. Respondents were more willing to view information from the hospital than to let the hospital view information from their own offices. CONCLUSION: This survey provided useful information on the perceived EPR needs of community-based family physicians. It will be repeated post-computerization.

Attitude to Computers↗

What is an electronic patient record?

While organizations develop their Electronic Patient Records, there will be a transition period during which computerized and paper records will both exist, possibly on multiple clinical information systems. This paper describes a model that defines the patient system of record and its constituent paper elements and electronic components. The model has been adopted by a large academic health science center for their development of an electronic patient record. The model has clarified which systems and data constitute the patient system of record and the standards and policies that apply to these systems.

Academic Medical Centers↗

[Comparison of two methods of age determination in teeth of known age from wild carnivores].

Two age-determining methods were conducted on representatives of known age from the Order Carnivora (4 red foxes, 3 tree martens, 3 stone martens, 2 racoons, 2 badgers, 2 polecat and one otter). Age determination employed with the aid of tooth wear nearly agrees with the real age of the animals. Dating based on the formation of the age-dependent cement zone coincided well with the known ages of the individual specimens. However, in real foxes the figure one must be added to the number of cementum layers counted determining the definitive age of individuals. For representation of the cementum layers transverse sections of the apical part of the tooth root of canini, P2 and P3, stained with methylene blue, should be used. It is important to note that the dentino-cemental line should not be considered when counting the year rings in the cement.

Age Determination by Teeth↗

Dental treatment of handicapped patients using endotracheal anesthesia.

Dental treatment using endotracheal anesthesia is indicated where acute odontogenic infections, accidental injuries, or multiple caries and periodontitis marginalis require surgical and/or restorative treatment. It is also indicated where it is not possible to use psychological support during local anesthesia or during premedication or analgosedation. Dental treatment of handicapped patients using endotracheal anesthesia is described, along with indication and frequency of such treatment. The state of the dentition is illustrated, along with its relationship to the oral hygiene the handicapped patients receive. The main points of the intraoperative dental procedures and the follow-up of patient care are reported. Postoperative dental or general medical complications have not occurred within the patient population under study.

Adolescent↗

An analysis of the paper-based health record: information content and its implications for electronic patient records.

An analysis of paper-based charting was carried out at Sunnybrook Health Sciences Center as a prelude to developing a strategic plan to implement an electronic patient record. A relational model of the Sunnybrook paper chart was developed, describing each of its forms in terms of specific data fields. Three hundred and forty nine different forms are in current use at Sunnybrook, containing 64 types of data fields such as Patient Demographics, Vital Signs, and Doctor's Orders. The extent of data field duplication at the level of hospital forms was significant. A Patient Demographics field was present on all forms and on all pages of a patient's chart, as would be expected. Twenty seven other fields were duplicated on more than ten different forms, including Working Diagnosis which was present on 110 forms, History of Past Illness on 42 forms, and History of Present Illness on 32 forms. Current Medications were recorded on 32 forms and Allergy fields were present on 29 separate forms. Only five data fields of the total 64 were present on only one form. The duplication of data fields within complete patient charts was then examined to confirm that data field duplication was occurring within the actual healthcare delivery process. Using the relational model of the charting system, 143 acute care in-patient encounters were abstracted into the database. The charts were selected randomly from each of the hospital inpatient services. The numbers and types of forms within each chart were recorded, amounting to 18,654 physical pages and using 165 of the different forms. The average in-patient encounter within the model was 130.4 pages long, with a minimum of 27 pages, a maximum of 559 pages, and containing on average 25.8 different forms. The duplication of data fields within actual charts followed a pattern similar to the duplication found on the forms. Initial diagnosis was present on an average of 20.4 pages within the charts, with a minimum of 2 pages and a maximum of 152 pages containing this data field. Other frequently occurring data fields included History of Past Illness present on an average of 12.2 pages per chart, History of present illness on 10.2 pages per chart, and allergies on an average of 9.1 pages per chart. The results obtained through the examination of Sunnybrook charts should be generalizable to most paper-based systems. This study did not measure the workload associated with duplicating chart data. however, the magnitude of the duplication seen in this study leaves little doubt that significant amounts of time could be saved with appropriate modification of health care delivery processes. Multiple copies of the same data field within a database are referred to as aliases of each other. This study demonstrates that hospital charts contain many copies of the same information, such as medication lists, allergies etc. Due to manual replication of data fields, there is no mechanism to ensure that each copy of a data element within a chart actually contains the same information. This aliasing of data through manual duplication compromises the integrity of data within paper-based charts. Decisions and therapy based upon contradictory or inaccurate data are likely to lead to inefficient or erroneous care delivery; this has significant implications for hospital liability and quality of patient care. A growing recognition of the costs and risks of data replication within paper-based charting systems is driving the healthcare industry toward Electronic Patient Record systems. Better quality patient care data, provided by computerized records, is likely to be necessary but not sufficient to improving the efficiency and effectiveness of the healthcare system. Intelligent application of this information will be essential.

Medical Records↗

[The histology of mastopathy and cumulative ipsilateral breast cancer sequence].

In a retrolective and follow-up study the ipsilateral cumulative risk of breast carcinoma after histological benign diseases in women under 66 years of age (n = 1397) is investigated. The subtypes are mastopathy I (= changes without proliferative lesions), mastopathy II (= proliferative lesions without atypia), and mastopathy III (id sunt atypical ductal and lobular hyperplasias). The cumulative risk with mastopathy I and II over a 15 year time period corresponds with the ordinary age related risk, the cumulative risk with mastopathy III is four times higher (p = 0.001). There is no difference between atypical ductal and lobular hyperplasia (p = 0.7). Women in reproductive age have a higher risk (p = 0.03), which exists even after a carcinoma-free survival of more than 10 years. The mastopathy is more a stigma for a higher breast cancer risk than a direct precancerous lesion.

Adolescent↗

Dyslexic children learn a new visual strategy for reading: a controlled experiment.

Recent studies by Geiger, Lettvin and Zegarra-Moran have proposed a new non-reading test for the diagnosis of dyslexia, and a new method for remediation. The latter involves the learning of a "visual strategy". On adult dyslexics the test was reliable and the remediation apparently effective. The purpose of this study is to confirm the usefulness of the remediation and test with children. Dyslexic children (3rd-6th grade) were divided into two groups. The experimental group (9) was given a new remedial regimen of practise. The control group (6) continued the remedial process given in their school. After 3 months of practising their separate regimens all the dyslexic children who were in the two groups were retested and compared. The "experimental" dyslexics improved in reading by 1.22 grade level on average while the "control" dyslexics improved by 0.17 grade on average. The form-resolving field (FRF) plots narrowed significantly for the experimental dyslexics while they changed little for the control dyslexics. At the end of the second testing the control dyslexics were also given the new regimen of practise. Five months later all the dyslexic children were tested for the third time. The initial control dyslexics who later practised the regimen (2) improved in reading by 2-2.5 grades and their FRF plot narrowed. The experimental dyslexics continued to improve yet further. All the dyslexic who practised the new regimen started at an average of 2.5 grades behind their expected grade/age level and after 8 months were at an average 0.75 grades behind their expected grade/age level. This is on average 1.75 grade level improvement in reading within 8 months, a rate of improvement larger than that of ordinary reading subjects. The dyslexic children were compared with matched grade/age ordinary reading children for reference. The study confirms the usefulness of the test and the applicability of the remediation method for children. It also shows that improvement under that method is quite rapid.

Child↗

Visual recognition in the peripheral field: letters versus symbols and adults versus children.

The plot of the form-resolving field (FRF) was obtained by tachistoscopically presenting two figures in each stimulus, one in the center of gaze and the other in the peripheral field. The figures in the periphery were placed at various eccentricities in different presentations. The ensuing plot of average letter recognition as a function of eccentricity is the FRF. Only the horizontal components of the FRFs were used in the comparisons. Three sets of figures were used as stimuli: regular-size letters, large-size letters, and symbols. Three groups of subjects were compared: adult ordinary readers, reading children, and pre-reading-age children. The last were tested with symbols only. In letter recognition, the FRFs for young and adult ordinary readers are similar and fall off monotonically and symmetrically with eccentricity, hence conforming with the first Aubert-Foerster law (1857). However, the FRFs tested with symbols are narrower than those tested with letters of the same sizes and stroke widths, which is not in accordance with the first Aubert-Foerster law. In addition, the FRFs of symbols are different for each subject group. It is suggested that recognition in the peripheral field is not determined by visual acuity alone; rather, it is further confined or determined by the visual strategy employed to accomplish the task, and its associated distribution of lateral masking.

Adult↗

[Micromorphological studies of the blood vessels of the dental pulp of small ruminants].

The blood vascular supply of the dental pulp of 15 domestic sheep of varying age and sex was investigated using light and electron microscopy. The pulp vascular system is showing arterioles with a media of varying thickness and with endothelial cells of variable structure. In the transitional zone between crown and root pulp, the arterioles are taking a typical S- or U-shaped course. The capillary network of the crown pulp is denser and more regular than that in the root pulp. In addition to the capillaries lined by a continuous endothelial tube, there may be others with a typically fenestrated endothelial lining. Specialised vascular structures of the peripheral blood vessels, especially arterio-venous anastomoses as described in man, have not been observed in the sheep.

Animals↗

[Scanning electron microscopic studies of the odontoblasts and the pulpodentinal border in domestic sheep (O. ammon aries Linnaeus, 1758)].

In order to investigate odontoblasts and predentin surfaces using SEM techniques, teeth of sheep with one or several roots were subjected to critical point drying. The odontoblasts of the root pulp are distinguished in their shape and arrangement pattern from those in the crown pulp. They regularly are detaching only one process of Tomes, which is extending up to the border between dentin and enamel and which shows a dendritic ramification in the dentin next to the enamel. The distal cell portions of the odontoblasts are joined together by a system of terminal bars. The collagen structures observed between the odontoblasts and predentin are considered to be von Korff's fibres as found in man.

Animals↗

[Micromorphologic studies of the odontoblasts of sheep in different development and maturation stages].

The fine tissue structure of ovine odontoblasts was studied in various developmental and maturational stages. Odontoblasts differentiate from the peripherally-located mesenchymal cells of the dental papilla. On the basis of cytological parameters, it was possible to divide the odontoblasts into the following groups: pre-odontoblasts, juvenile (light) odontoblasts and mature (dark) odontoblasts. The three maturational stages of odontoblasts exhibit substantial differences with respect to their form and to the number and arrangement of their cytoplasmatic organelles. Structural differences in the three cell types appear to be closely correlated to the level of cellular activity.

Animals↗

[Fine tissue studies of the nerve supply to the dental pulp in domestic sheep (O. ammon aries Linné, 1758)].

The nerve supply of the pulp was investigated in 17 sheep of various breeds and age groups belonging to both sexes, using light and electron microscopy. The following results were obtained: The dental pulp of sheep is supplied with myelinated and unmyelinated nerve fibres. The subodontoblastic plexus of Raschkow, as found in man, is absent in sheep. Single axons may be found in the predentine between the odontoblasts and near Tomes' processes. The rare occurrence of both subodontoblastic nerve fibres and cells of the immune system in the ovine pulp is discussed in relation to evolutionary processes, in light of the fact that sheep are relatively resistant to caries.

Animals↗