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Biomedical subjects

K Taylor

Publications and source records attributed to K Taylor.

At least 217 records · Page 12Linked to original sources

Segregation of the growth slowing effects of valproic acid from phenytoin and carbamazepine on lymphoid tumor cells.

One human and six murine tumor cell lines of lymphoid origin were assessed for growth in the presence of three commonly used antiepileptic drugs (AEDs). All seven lines were sensitive to the growth slowing effects of phenytoin (PHT) and carbamazepine (CBZ). Six lines showed a similar effect when exposed to valproic acid (VPA), while one murine B cell line was resistant to inhibition of growth by VPA.

Carbamazepine↗

Cytogenetic effects of singlet oxygen.

Singlet oxygen was generated in the gas phase at atmospheric pressure by the method of heterogeneous photosensitization. In vitro exposure of human lung WI-38 fibroblasts to gas-phase singlet oxygen resulted in sister chromatid exchange.

Cell Line↗

Kallmann syndrome due to a translocation resulting in an X/Y fusion gene.

The X-linked Kallmann syndrome gene was recently cloned and homologous sequences of unknown functional significance identified on the Y chromosome. We now describe a patient with Kallmann syndrome carrying an X;Y translocation resulting from abnormal pairing and precise recombination between the X-linked Kallmann syndrome gene and its homologue on the Y. The translocation created a recombinant, non-functional Kallmann syndrome gene identical to the normal X-linked gene with the exception of the 3' end which is derived from the Y. Our findings indicate that the 3' portion of the Kallmann syndrome gene is essential for its function and cannot be substituted by the Y-derived homologous region, although a 'position' effect remains a formal possibility.

Amino Acid Sequence↗

Effect of a single 30-minute treatment of high voltage pulsed current on edema formation in frog hind limbs.

The purpose of this study was to investigate the effect of a single treatment of high voltage pulsed current (HVPC) on edema formation. Twenty-four frogs were anesthetized, and both hind limbs of each frog were traumatized by impact. Limb volumes were measured by water displacement immediately before and after trauma and at predetermined intervals for 24.0 hours posttrauma. One limb of each frog was randomly selected to receive 30 minutes of continuous, 120-pulse per second, cathodal HVPC at voltages 10% less than motor threshold levels. Data were analyzed by an analysis of variance for repeated measures. Sources of significant differences were determined by paired t tests (probability values determined by Bonferroni adjustment). A single 30-minute application of HVPC significantly curbed edema formation for between 4.0 and 7.5 hours following treatment (ie, volumes of treated limbs were significantly less than those of untreated limbs). These results suggest that regimens currently applied to humans (ie, one treatment per day or three times per week) may be insufficiently aggressive to provide sustained treatment effects.

Animals↗

Effect of electrically induced muscle contractions on posttraumatic edema formation in frog hind limbs.

We tested the hypothesis that repeated muscle contractions induced by high voltage pulsed current (HVPC) would limit volume increases in traumatized frog hind limbs. Twelve frogs were anesthetized, and both hind limbs of each frog were traumatized by impact. Limb volumes were measured via water displacement over a 24-hour period. Four 30-minute treatments of continuous 1-pulse per second HVPC were applied to one limb selected randomly. Stimulation produced muscle contractions that resulted in minimal joint movements. Volume changes from pretrauma limb volumes (in milliliters per kilogram) were analyzed by an analysis of variance for repeated measures. Our hypothesis was rejected (ie, repeated muscle contractions, as induced in this study, did not limit posttraumatic edema formation in frogs). Further investigation of the relative influences of limb position and varying pulse rates, pulse durations, and intensities of HVPC on edema formation may provide valuable insights on effective treatment of edema in humans.

Animals↗

Phospholipid-containing toxic malaria antigens induce hypoglycaemia.

Hypoglycaemia is associated with severe malaria and is an important prognostic indicator. Molecules liberated during overnight incubation of erythrocytes infected with Plasmodium yoelii induce marked hypoglycaemia in normal mice, with a delayed time course compared with insulin; some, though weaker, activity could also be obtained by overnight incubation of uninfected erythrocytes. The active component shares many properties with the phospholipid-containing molecules which we have previously shown to be toxic and to induce the release of tumour necrosis factor (TNF) from macrophages. However a MoAb which neutralizes the cytotoxicity of tumour necrosis factor in vitro did not prevent this induction of hypoglycaemia, whereas antiserum against the toxic antigens did, as did immunization of normal (but not the immunoglobulin-deficient SCID) mice with the same material. Furthermore, normal mice injected with the antigens after immunization with phosphatidyl inositol or inositol monophosphate did not develop hypoglycaemia; the latter compound was also inhibitory when mixed with the antigens before injection. These compounds were previously shown to block the induction of TNF by the antigens and to induce the production of inhibitory antibodies. The role of these molecules in the etiology of the hypoglycaemia of malaria is discussed.

Animals↗

Monoclonal large granular lymphocyte proliferation in SLE with HTLV-I seroreactivity.

A 60-year-old part Aboriginal woman was observed to develop severe neutropenia and a large granular lymphocyte (LGL) proliferation five years after the diagnosis of systemic lupus erythematosus (SLE). Monoclonality of the CD3+, CD4-, CD8+ LGL population was confirmed using the novel approach of X-linked restriction fragment length polymorphism (RFLP) analysis. Indeterminate HTLV-I serology was present. The patient responded to steroid therapy. LGL proliferation in the setting of SLE and the use of X-linked RFLP analysis to define LGL clonality have not previously been reported.

Antibodies, Monoclonal↗

Proportional assist ventilation. Results of an initial clinical trial.

The response to proportional assist ventilation (PAV) was tested in four normal subjects during heavy exercise and in five ventilator-dependent patients recovering from assorted medical disorders. The apparatus consisted of a rolling-seal piston coupled to a motor that generated pressure in proportion to inspired flow and inspired volume, with the gains adjusted such that the proportionality between airway pressure (Paw) and instantaneous patient-generated pressure (Pmus) was approximately 1:1 (i.e., machine-amplified patient effort by a factor of 2). Normal subjects responded to PAV by decreasing their own effort, as judged from esophageal pressure, such that the changes in ventilation and breathing pattern were rather small (VE: 64.8 +/- 3.6 during PAV versus 56.0 +/- 4.3, p less than 0.01; VT: 2.39 +/- 0.24 versus 2.02 +/- 0.17, p less than 0.05; f: 27.5 +/- 1.9 versus 28.0 +/- 2.2, NS). In patients, elastance ranged from 20 to 35 cm H2O cm/L, resistance ranged from 5 to 10 cm H2O/L/s, and maximal inspiratory pressure ranged from -16 to -65 cm H2O. After a period of observation during synchronized intermittent mechanical ventilation (SIMV) the patient was switched to PAV and maintained on it for 1 to 3 h. No patient had to be replaced on SIMV because of discomfort or deterioration in any of the monitored variables. During PAV peak airway pressure was less than half the value observed with the IMV breaths (16.6 +/- 2.4 versus 35.4 +/- 3.4 cm H2O, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Ferrocenopapain, an organometallic protein formed by site-specific inactivation of papain using chloroacetylferrocene.

Papain is rapidly, specifically and irreversibly inactivated by chloroacetylferrocene in a time-dependent, two-stage process which involves initial, physical complexation between the enzyme and the organometallic reagent followed by chemical reaction. The kinetics of the process show saturation kinetics with respect to inactivator concentration. The modification occurs with a 1:1 stoichiometry and the degree of loss of enzymatic activity is directly reflected in the loss of thiol groups in the active-site that are accessible to Ellman's reagent. The modification is faster at higher pH. The ferrocenium ion of the modified papain can be generated at low pH by anaerobic treatment with ferric nitrate and shows a 180 percent increased lifetime at pH 3.3 compared to the acetylferrocenium ion under identical conditions. The spectral properties of the ferrocenopapain indicate that the ferrocene is in an unusual environment at the protein active-site and the implications of this are discussed.

Cysteine↗

All-trans retinoic acid in the treatment of acute promyelocytic leukaemia.

All-trans-retinoic acid (ATRA) is known to induce differentiation of promyelocytes in vitro and also to induce remission of acute promyelocytic leukaemia in vivo. We treated 11 patients with poor prognosis acute promyelocytic leukaemia (APL) with ATRA and obtained seven complete and one partial remission. Remissions took one to three months to achieve and were associated with adverse effects including dry skin and bone pain. In eight patients the white cell count rose above 20 x 10(9)/L within the first ten days of retinoic acid treatment and this was associated with the development of pulmonary leukostasis in three patients which was fatal in one. Another two patients died of intracranial haemorrhage also within the first ten days. ATRA is a promising new agent in the induction therapy of this particular category of acute leukaemia.

Adult↗

Mechanisms of plasma membrane protein degradation: recycling proteins are degraded more rapidly than those confined to the cell surface.

Plasma membrane proteins of intact mouse 3T3 fibroblasts and H4-II-E-C3 hepatoma cells were separated into two groups based on their compartmentation between the cell surface and an intracellular compartment accessible at 20 degrees C but not at 0 degrees C. One group was derivatized at 0 degrees C with sulfosuccinimidyl 2-(biotinamido)ethyl-1,3-dithiopropionate but not at 20 degrees C. The second group was derivatized at 20 degrees C as well as at 0 degrees C. Derivatized proteins were isolated from 35S-labeled cells on streptavidin/agarose and resolved by two-dimensional PAGE. With few exceptions, pulse-chase experiments revealed that those proteins confined exclusively to the cell surface turned over slowly (t1/2, greater than 75 h), while those bimodally compartmentalized between the cell surface and the 20 degrees C accessible compartment were degraded more rapidly (t1/2, less than 31 h). These observations suggest a mechanism to explain the varied metabolic stability of plasma membrane proteins in which the half-life of each protein is determined by the proportion of time spent in the endocytic compartment.

Animals↗

Comparison of ZFY and ZFX gene structure and analysis of alternative 3' untranslated regions of ZFY.

We have cloned and sequenced transcripts from the X- and Y-linked zinc-finger genes ZFX and ZFY respectively and discuss a possible mechanism of post-transcriptional control by which these genes can be widely expressed but translated in only specific tissues. We report the identification of a novel 3'UTR (untranslated region) present in ZFY which is highly conserved among primates and contains a series of motifs implicated as mRNA instability determinants. These sequences can be substantially removed by polyadenylation directed from consensus (AATAAA) and non-consensus (AATATAAA) sequences in adult testis. The DNA-binding domains of the ZFY and ZFX proteins are compared using present models for zinc-finger/DNA interactions. Additionally, the genomic organisation of the ZFY coding sequence is presented as compared to that of ZFX.

Amino Acid Sequence↗

Laser success.

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Humans↗

Effect of organic anions on the crystallization of the Ca2(+)-ATPase of muscle sarcoplasmic reticulum.

The effect of varying the solute species on the crystallization of the Ca2(+)-ATPase from rabbit muscle reticulum (SR) is reported. We have found that substitution of KCl with salts of organic acids in the crystallization protocol reported by Pikula et al. has a profound effect on the size of two-dimensional crystalline arrays. Crystalline arrays of up to 3 microns diameter have been obtained by incubating purified calcium ATPase in standard crystallization medium but with 0.8 M sodium propionate substituted for KCl. These two-dimensional (2-D) arrays display a reduced tendency to stack in addition to having larger planar dimensions. Increasing the KCl concentration does not have the same effect on stacking or crystal growth that sodium propionate has. The production of 2-D sheets has some dependence on the hydrocarbon chain length of the salt because crystals formed in propionate were larger and less stacked than those formed in acetate or formate. There seems to be no dependence on cation. These observations suggest that in addition to reducing the forces that lead to stacking of the sheets, propionate may facilitate incorporation of the detergent-solubilized protein into the 2-D sheet.

Acetates↗

Psychological effects of custody disputes on children.

This two-group, repeated measures examination of the psychological impact of child custody contests on children reports a subset of data from an ongoing longitudinal study of 95 children and their parents from 43 divorcing families. The authors report clinical observations concerning children's experience of custody litigation, as well as comparisons of baseline and post-test responses of contested and uncontested groups on measures of locus of control, separation anxiety and family concept. Contested children exhibited significantly greater internality of control orientation than the normative sample. Contested children's test scores also suggested significantly less separation anxiety and significantly more positive family concept than the uncontested group at post-test. The implications of these unanticipated findings are discussed.

Adult↗

Stringent control of replication of plasmids derived from coliphage lambda.

The first events of lambda plasmid replication in vivo, which probably regulate this process, are the transcriptional activation of the origin of replication by RNA polymerase and the binding of the initiator protein, lambda O, to this nucleotide sequence. The lambda O protein is known for its rapid proteolytic degradation; hence amino acid starvation of Escherichia coli should result in inhibition of lambda plasmid replication caused by inhibition of protein synthesis. However, contrary to this prediction, we found that lambda plasmid replication, as measured by the increase in plasmid content per bacterial mass, proceeds for hours in an amino acid-starved, relaxed mutant, whereas it is inhibited in its wild-type stringent partner. lambda plasmid replication in amino acid-starved, relaxed cells reveals absolute lambda O dependence and is not inhibited by chloramphenicol at 200 micrograms/ml. This process also occurs in wild-type cells treated with chloramphenicol. We conclude that lambda plasmid replication is under stringent control, probably as a result of the action of ppGpp, the indirect product of the relA gene, on RNA polymerase. The problem of stability of the lambda O initiator protein is discussed.

Bacteriophage lambda↗