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Biomedical subjects

J Nichols

Publications and source records attributed to J Nichols.

At least 55 records · Page 3Linked to original sources
PubMed1995

Increased DT-diaphorase activity in transformed and tumorigenic pancreatic acinar cells.

Pancreatic acinar cells from rats treated in vitro with 5-azacytidine and/or transfected with an activated c-H-ras demonstrated transformation and tumorigenic phenotypes. DT-diaphorase (NAD(P)H:quinone oxidoreductase) activity was determined in these non-tumorigenic (3AP) and tumorigenic cells (T3AP and T5AM). T5AM cells were those treated with 5-azacytidine and further treated with N'-methyl-N'-nitro-nitrosoguanidine. Higher levels of enzyme activity were found in transformed cells when compared to that in control cells (> 15-fold, 3AP cells; > 40-fold, T3AP cells; > 20-fold T5AM cells). In contrast, NADPH-cytochrome c reductase activity was decreased in transformed cells (> 10-fold, 3AP cells; > 20-fold, T3AP cells; > 10-fold, T5AM cells). These studies demonstrated that pancreatic acinar cells are capable of undergoing alterations in enzyme activity patterns when transformed and that DT-diaphorase may be a good marker for malignant transformation.

Animals↗
PubMed1995

Effect of dietary restriction on glutathione S-transferase activity specific toward aflatoxin B1-8,9-epoxide.

Dietary restriction (DR) reduced the metabolic activation of aflatoxin B1 (AFB1) in rats. This reduction may be attributed to the decrease of cytochrome P-450-mediated AFB1 epoxidation and/or increase in the detoxification of AFB1 catalyzed by hepatic glutathione S-transferase (GST) and other phase II detoxification enzymes. In this study the effect of DR on male rat liver cytosolic GST activity toward AFB1-8,9-epoxide was studied. The chemically-synthesized AFB1-8,9-epoxide was used as the substrate in this assay, and the formation of AFB1-GSH conjugate was analyzed by HPLC. Male Fischer 344 rats fed DR diets (60% of the food consumption of ad libitum (AL)-fed rats) showed a 2.4-fold increase in GST activity when AFB1-epoxide was used as the substrate. The results from the enzyme kinetic study showed that DR increased Vmax of the liver cytosolic GST but not the Km. Acute DR has little or no impact on GST activity when 1-chloro-2,4-dinitrobenzene and 2,4-dichloronitrobenzene were used as substrates. The mouse liver GST activity toward AFB1-epoxide was 3-fold greater than that of phenobarbital-induced rats, 4.5-fold greater than DR rats, and 14.7-fold greater than the GST activity of AL rats. This direct assay of liver GST activity using AFB1-epoxide as the substrate is useful for studying AFB1-induced biomarkers, such as AFB1-GSH conjugation and AFB1-DNA adducts.

Aflatoxin B1↗
PubMed1995

Atlantooccipital dislocation: a case report.

We report on a child who suffered an atlantooccipital dislocation and survived. The patient required tracheostomy and feeding gastrostomy due to retropharyngeal swelling from a traumatic pseudomeningocele. He later underwent fusion of his occiput to C3. The complications of such an injury and the anesthetic management are discussed.

Anesthesia↗
PubMed1995

Isometric cervical extension strength of recreational and experienced cyclists.

The effect for cyclists of the typical forward sitting position on neck strength and its possible relationship to neck pain have not been examined. The purpose of this study was to measure the peak isometric cervical extension strength (PICES) of both recreational and experienced road cyclists and to compare these values to those of noncyclists. Subjects, 45 men between the ages of 18 and 40, were tested for voluntary PICES through a 126 degrees range of motion on a MedX cervical extension machine. No significant differences were found between the three groups in PICES at any angle. When expressed relative to body weight, significant differences in PICES were found at 126 degrees between the control group and the recreational cyclist group (p < 0.05), and between the control group and the experienced cyclist group (p < 0.01), but not at any other angle. Furthermore, no significant differences in strength were found between cyclists experiencing neck pain and those who did not. These data indicate that the cervical muscles of cyclists have not adapted by increasing maximal isometric strength above that of noncyclists, and that the neck pain frequently reported may be due to fatigue from sustained muscular contractions associated with time spent cycling, rather than from muscle weakness.

Adolescent↗
PubMed1995

Measurement of wound healing by image analysis.

Chronic wound healing is a major health problem consuming more than $10 Billion/year. Noninvasive measurements of wounds are critical for evaluation of different therapies. In this paper, we present two image processing methods which can be used to compare the effects of different dressings on pig skin wounds. In the first part, the healing process is monitored by area measurements. Using thresholding the wound areas are calculated by pixel counting and corrected with perspective scaling. This technique showed good correlation with manual area measurements. In the second part, 3 D coordinates of the selected wound points are calculated using triangulation from a single colored image coordinates. Such a 3 dimensional image reconstruction from a single camera is made possible by projecting a structured light pattern onto the skin. In this study, a unique pattern consisting of colored dots is used. This color-coded pattern provides many advantages over widely used grid patterns: it is not necessary to see the whole image to recognize the points, since every dot can be identified correctly from its closest eight neighbors, eliminating occlusion problems. Our approach to structured light also mitigates the problem of motion in a subject, since all the coding information is contained in a single image.

Animals↗
PubMed1994

Dicistronic targeting constructs: reporters and modifiers of mammalian gene expression.

To investigate the activity of candidate regulatory molecules in mammalian embryogenesis, we have developed a general strategy for modifying and reporting resident chromosomal gene expression. The picornaviral internal ribosome-entry site was incorporated into gene targeting constructs to provide cap-independent translation of a selectable marker from fusion transcripts generated following homologous recombination. These promoterless constructs were highly efficient and have been used both to inactivate the stem-cell-specific transcription factor Oct-4 and to introduce a quantitative regulatory modification into the gene for a stem-cell maintenance factor, differentiation-inhibiting activity. In addition, the inclusion of a beta-galactosidase reporter gene in the constructs enabled accurate and sensitive detection of cellular sites of transcription. This has allowed visualization of putative "stem-cell niches" in which sources of elevated expression of differentiation-inhibiting activity were localized to the differentiated cells surrounding colonies of stem cells.

Animals↗
PubMed1994

Derivation of germline competent embryonic stem cells with a combination of interleukin-6 and soluble interleukin-6 receptor.

In this report we document the derivation of pluripotential embryonic stem (ES) cells in the absence of a feeder layer by supplementation of culture media with either ciliary neurotrophic factor or oncostatin M, or with a combination of interleukin-6 (IL-6) plus soluble interleukin-6 receptor (sIL-6R). These factors all activate gp130-associated signaling processes, as does the previously characterized ES cell maintenance factor Differentiation Inhibiting Activity (Leukemia Inhibitory Factor). In particular, the IL-6/sIL-6R complex is thought to act exclusively through gp130. All ES cell lines derived using IL-6/sIL-6R contributed extensively to chimeras and were transmitted through the germline at high frequency. These findings point to a pivotal role for gp130 in ES cell propagation and may be relevant to attempts to derive ES cells from species other than mouse.

Animals↗
PubMed1994

Peripheral blood hairy cell leukemia cells express only low affinity IL-2 receptors.

Purified leukemia cells from three patients with hairy cell leukemia were studied for IL-2 receptor status. All samples expressed the p55IL-2 receptor subunit. However, none demonstrated sensitivity to the IL-2-diphtheria toxin conjugate, DAB486IL-2, which shows selective cytotoxicity for high affinity IL-2 receptor-bearing cells. In the one case studied with 125I-IL-2 binding, only low affinity IL-2 receptors were noted. These data suggest that hairy cell leukemia cells express only low affinity IL-2 receptors and are insensitive to DAB486IL-2.

Diphtheria Toxin↗
PubMed1994

PHA induces IL-2 receptors on B-CLL cells and is a potential biological response modifier for the LIL-2-diphtheria toxin, DAB486IL-2.

DAB486IL-2 is an IL-2-diphtheria toxin conjugate which was developed to be specifically cytotoxic to cells bearing high affinity IL-2 receptors. The high affinity IL-2 receptor is a heterodimer comprising p55 and p75 subunits. While the p75 subunit appears to be ubiquitously expressed among the common North American leukemias and lymphomas, the p55 subunit is more restricted in its expression. To broaden the therapeutic relevance of the DAB486IL-2 we have sought physiologically feasible inducers of the p55 IL-2 receptor subunit. This report describes that PHA, in vitro, induces the p55 IL-2 receptor subunit on initially p55-negative B-CLL cells and converts toxin-insensitive leukemia cells to a toxin-sensitive state.

Diphtheria Toxin↗
PubMed1994

The trigger film in nurse education.

The use of video in education is now common place. Most Colleges of Nursing and Midwifery have access to the equipment for making and/or showing their own films. Video cannot be used indiscriminately and assumed to be effective. Many educational videos are entertaining but encourage a passive audience. As a result the materials may be enjoyable but the learning achieved, disappointing. An application of video that involves the student in active learning is the trigger film. This is a short piece of film, generally only a few minutes long whose aim is to stimulate and provoke learning. It is a unique form of film possessing special characteristics. The use of the trigger film in other areas of education is documented but its application to nurse education not widely explored. A trigger film has been produced by the author and used with nursing students (RN/Dip HE) to explore professional issues. The trigger film has been found to be an excellent stimulus for discussion and particularly effective for analysis of complex issues. Evaluation by students has been overwhelmingly positive. The trigger film lends itself to exploitation within nurse education. It is particularly useful for learning within the Affective Domain (Baud & Pearson 1979). This paper will discuss the use of video in nurse education, the concept of the trigger film and the use and evaluation of the authors own film.

Decision Making↗
PubMed1994

Maintenance of the pluripotential phenotype of embryonic stem cells through direct activation of gp130 signalling pathways.

Propagation of the undifferentiated pluripotential phenotype of embryonic stem (ES) cells is dependent on the cytokine differentiation inhibiting activity/leukemia inhibitory factor (DIA/LIF). The DIA/LIF receptor complex is a heterodimer of DIA/LIF receptor (DIA/LIF-R) and gp130. The latter is also a component of the interleukin-6 (IL-6) receptor complex. We report that a combination of IL-6 and soluble IL-6 receptor (sIL-6R), which can induce homodimerisation of gp130 and activation of signalling processes, sustains self-renewal of pluripotential ES cells. Our findings indicate that the IL-6/sIL-6R complex acts on ES cells through gp130 alone, bypassing DIA/LIF-R, and therefore implicate gp130 as the key component in the signalling pathway responsible for stem cell renewal.

Amino Acid Sequence↗
PubMed1994

Traumatic atlantooccipital dislocation injury in children.

The tragedy of trauma turns into triumph when the surgery team members' efforts result in victory for the patient. Nowhere is this more true than in successful pediatric trauma care. Giving a child a second chance at life and the family an opportunity for a new beginning is the highest reward for the trauma team's years of professional training and practice. Traumatic atlantoocipital dislocation injury usually results in death, but recent neurosurgery trauma advances are increasing pediatric survival rates.

Atlanto-Occipital Joint↗
PubMed1994

Three-dimensional visualization of physiologically based kinetic model outputs.

Outputs from a physiologically based toxicokinetic (PB-TK) model for fish were visualized by mapping time-series data for specific tissues onto a three-dimensional representation of a rainbow trout. The trout representation was generated in stepwise fashion: 1) cross-section images were obtained from an anesthetized fish using a magnetic resonance imaging system, 2) images were processed to classify tissue types and eliminate unnecessary detail. 3) processed images were imported to a visualization software package (Application Visualization System) to create a three-dimensional representation of the fish, encapsulating five volumes corresponding to the liver, kidney, muscle, gastrointestinal tract, and fat, Kinetic data for the disposition of pentachloroethane in trout were generated using a PB-TK model. Model outputs were mapped onto corresponding tissues volumes, representing chemical concentration as color intensity. The workstation software was then used to animate the images, illustration the accumulation of pentachloroethane in each tissue during a continuous branchial (gill) exposure.

Animals↗
PubMed1993

Expression of alternative forms of differentiation inhibiting activity (DIA/LIF) during murine embryogenesis and in neonatal and adult tissues.

Differentiation inhibiting activity/leukaemia inhibitory factor (DIA/LIF) is a pleiotropic cytokine which has been implicated in a variety of developmental and physiological processes in mammals due to its broad range of biological activities in vitro. A role in very early development is suggested by the requirement for DIA/LIF to support the self-renewal of cultured embryonic stem (ES) cells. Other data point to potential roles in the establishment and maintenance of primordial germ cells, in osteogenesis and in haematopoiesis, and possibly in neuronal specification. DIA/LIF may also act as a mediator of the hepatic acute phase response. In the present study the expression of DIA/LIF transcripts during murine development and in adult mice has been determined using a highly sensitive ribonuclease protection analysis. In contrast to previous reports, it is apparent that DIA/LIF transcripts are present at low levels in many adult mouse tissues. Higher levels of expression are observed in skin, lung, intestine, and uterus. Elevated amounts of mRNA are also found in certain foetal tissue during late gestation and neonatally. In earlier embryogenesis, however, DIA/LIF mRNA is produced primarily in extraembryonic tissues. The alternative transcripts which produce either soluble or matrix-associated DIA/LIF exhibit overlapping but non-identical patterns of expression, consistent with the proposition that the two isoforms may have distinct biological functions. These findings are suggestive of widespread roles for DIA/LIF in vivo and are discussed in the light of available data on the phenotype of homozygous DIA/LIF-deficient mice.

Aging↗
PubMed1993

A study of respiratory infections in a healthy adult population during the 1987 Australian winter.

During the 1987 Australian winter, respiratory illness patterns were studied in a population of 454 healthy adults, aged 18-59, over a period of 45 days. These patterns were matched with data obtained from laboratory diagnoses for respiratory viruses, Mycoplasma pneumoniae and bacteria. Influenza B/1/86 was by far the most prevalent pathogen but other viruses including influenza A, paramyxoviruses, respiratory syncytial virus and coronavirus OC-43 were also present, either alone or in combination during the sampling period. Overall, 92 males and 101 females experienced one episode, 12 males and 22 females experienced two episodes and four females experienced three episodes. However, there were only 52 instances of viral or M. pneumoniae infections, of which 37 had a defined aetiology, while the remainder were clinically silent. No bacterial pathogens could be detected from throat swabs taken from 15 of 37 volunteers in whom a viral infection was detected, or from 43 of 70 volunteers who did not experience such infections. The study indicates that major deficiencies in our understanding of the aetiology of respiratory viral illness are probably due to methodological problems in obtaining laboratory diagnoses for many respiratory viruses, and that great difficulties exist in establishing an aetiology for respiratory infections based upon clinical symptoms alone.

Adolescent↗
PubMed1993

Interleukin-2 receptor-directed therapies: antibody-or cytokine-based targeting molecules.

With the exception of certain hematologic malignancies, the high affinity interleukin-2 (IL-2) receptor is only transiently expressed during the brief antigen-triggered proliferative burst of lymphocytes. Hence, we wondered whether administration of anti-IL-2 receptor (IL-2R) monoclonal antibody (mAb) or chimeric IL-2 toxins would provide a utilitarian way to achieve immunosuppression aimed directly at activated lymphocytes, or whether this approach could be used to treat IL-2R+ leukemia/lymphoma. Studies in preclinical autoimmune and transplant models indicate that this approach can be effective. The results of open, uncontrolled studies provide preliminary evidence that a chimeric IL-2 toxin is well tolerated at doses that may induce improvement in patients with IL-2R+ leukemia/lymphoma, as well as in patients with refractory rheumatoid arthritis or new-onset diabetes mellitus.

Animals↗