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Biomedical subjects

K Taylor

Publications and source records attributed to K Taylor.

At least 127 records · Page 7Linked to original sources

Molecular mechanism of heat shock-provoked disassembly of the coliphage lambda replication complex.

We have found previously that, in contrast to the free O initiator protein of lambda phage or plasmid rapidly degraded by the Escherichia coli ClpP/ClpX protease, the lambdaO present in the replication complex (RC) is protected from proteolysis. However, in cells growing in a complete medium, a temperature shift from 30 to 43 degrees C resulted in the decay of the lambdaO fraction, which indicated disassembly of RC. This process occurred due to heat shock induction of the groE operon, coding for molecular chaperones of the Hsp60 system. Here we demonstrate that an increase in the cellular concentration of GroEL and GroES proteins is not in itself sufficient to cause RC disassembly. Another requirement is a DNA gyrase-mediated negative resupercoiling of lambda plasmid DNA, which counteracts DNA relaxation and starts to dominate 10 min after the temperature upshift. We presume that RC dissociates from lambda DNA during the negative resupercoiling, becoming susceptible to the subsequent action of GroELS and ClpP/ClpX proteins. In contrast to lambda cro+, in lambda cro- plasmid-harboring cells, the RC reveals heat shock resistance. After temperature upshift of the lambda crots plasmid-harboring cells, a Cro repressor-independent control of lambda DNA replication and heat shock resistance of RC are established before the period of DNA gyrase-mediated negative supercoiling. We suggest that the tight binding of RC to lambda DNA is due to interaction of RC with other DNA-bound proteins, and is related to the molecular basis of the lambda cro- plasmid replication control.

ATPases Associated with Diverse Cellular Activitie↗

Simulation applied to health services: opportunities for applying the system dynamics approach.

The aim of this essay is to raise awareness and broaden understanding within the health services community of the system dynamics (SD) simulation approach to policy analysis. The application of simulation in health services is reviewed. A comparison is made between the SD and traditional simulation approaches and is illustrated by considering reductions in waiting times for coronary heart disease treatment. Traditionally, simulation studies have tended to focus on the analysis of localized decisions and therefore on problems orientated towards individual patients. Although these methods are extremely powerful and effective, there is scope for an alternative modelling approach which is based on a more holistic perspective; SD is one such approach. It can assist in the design of robust policies by supporting debate on how the underlying structure might influence the evolutionary behaviour of a system. Using this method we can consider the time variation both of tangibles, such as waiting times and health care costs, and intangibles, such as patient anxiety and the effects of various pressures on purchasing decisions. We propose that SD holds great potential in assisting policy formation in health care.

Computer Simulation↗

Effects of the endogenous clock and sleep time on melatonin, insulin, glucose and lipid metabolism.

This study was undertaken to determine whether the internal clock contributes to the hormone and metabolic responses following food, in an experiment designed to dissociate internal clock effects from other factors. Nine female subjects participated. They lived indoors for 31 days with normal time cues, including the natural light: darkness cycle. For 7 days they retired to bed from 0000 h to 0800 h. They then underwent a 26-h 'constant routine' (CR) starting at 0800 h, being seated awake in dim light with hourly 88 Kcal drinks. They then lived on an imposed 27-h day (18 h of wakefulness, 9 h allowed for sleep), for a total of 27 days. A second 26-h CR, starting at 2200 h, was completed. During each CR salivary melatonin and plasma glucose, triacylglycerol (TAG), non-essential fatty acids (NEFA), insulin, gastric inhibitory peptide (GIP) and glucagon-like peptide-1 (GLP-1) were measured hourly. Melatonin and body temperature data indicated no shift in the endogenous clock during the 27-h imposed schedule. Postprandial NEFA, GIP and GLP-1 showed no consistent effects. Glucose, TAG and insulin increased during the night in the first CR. There was a significant effect of both the endogenous clock and sleep for glucose and TAG, but not for insulin. These findings may be relevant to the known increased risk of cardiovascular disease amongst shift workers.

Adult↗

Natural justice.

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Employee Discipline↗

The cytotoxic action of 1,3,5-triazabicyclo[3.1.0]hexane-2,4-diones and 1,3,5-triazine-4,6-(1 H,5 H)-diones in murine and human tumor cells.

1,3,5-Triazabicyclo[3.1.0]hexane-2,4-diones proved to be potent antineoplastic and cytotoxic agents in murine and human cancer cells. In L1210 lymphoid leukemia cells DNA synthesis was significantly suppressed over 60 min by the agents from 25 to 100 microM. DNA synthesis was blocked at multiple sites including DNA polymerase alpha, ribonucleoside reductase, dihydrofolate reductase, PRPP-amido transferase, and nucleoside kinases which would be additive overall in suppressing DNA synthesis. The DNA molecule itself did not appear to be at target of the agents since no alkylation of nucleotide bases, intercalation between base-pairs or cross-linking of strands occurred after 24 h incubation at 100 microM. Nevertheless, L1210 DNA fragmentation did occur after 24 h incubation at 100 microM which is usually associated with tumor cell apoptosis.

Animals↗

A preliminary survey of oncologists' perceptions of quality of life information.

Quality of life (QOL) of cancer patients has become the focus of increasing research in oncology, and a frequently measured endpoint in clinical trials. Very little attention has been paid to the perspective of physicians on quality of life information, and its role in clinical decision-making. This report describes the findings of research focused on exploring the perspectives of physicians about quality of life information that is available for cancer patients. On the basis of qualitative data gathered through in-depth interviews with 60 oncologists in the first phase of this project, we have developed a self-administered questionnaire (MD-QOL survey) designed to assess oncologists' views on QOL. This survey was administered to an international group of gynecologic oncologists. The objectives of this study were to assess the face validity of the initial items in the MD-QOL, to expand the pool of items, and to assess the feasibility of utilizing a self-administered questionnaire to assess physicians' perspectives on QOL information. Twenty-eight oncologists responded to the questionnaire. The majority of respondents felt that QOL can be measured and that it should be measured from the patient's own perspective. Half of the physicians felt that currently available QOL information is useful in clinical practice. Ninety-three percent of respondents felt that the greatest benefit of QOL information is 'being able to treat the whole patient'. Forty one percent of respondents felt that length of survival is more important to patients than quality of life. However, only 7% of the respondents felt that the primary job of physicians is to save lives, and that QOL should not be a predominant concern for physicians. The inclusion of QOL in randomized trials was perceived as encouraging both patient and physician participation. The results of this survey are being used to further explore these critical issues.

Adult↗

Temporal bone analysis of patients with presbycusis reveals high frequency of mitochondrial mutations.

Presbycusis is a histologically and genetically heterogenous group of disorders, which lead to progressive, primarily sensorineural hearing loss with aging. Acquired mitochondrial DNA defects have been proposed as important determinants of aging, particularly in neuro-muscular tissues. The spiral ganglion and membranous labyrinth from archival temporal bones of 5 patients with presbycusis were examined for mutations within the mitochondrially-encoded cytochrome oxidase II gene. When compared to controls, results indicate that mitochondrial mutations in the peripheral auditory system occur commonly with age-related hearing loss, that there is great individual variability in both quantity and location of mutation accumulation, and that at least a proportion of presbycusis patients have a highly significant load of mutations in auditory tissue. This work supports the hypothesis that acquired mitochondrial mutations are a determinant of hearing loss in a subgroup of presbycusis patients.

Aged↗

Pulsatile and nonpulsatile perfusion: the continuing controversy.

This report discusses pulsatile and nonpulsatile perfusion with regard to hemodynamics, cell metabolism, and the visceral consequences of these forms of cardiopulmonary bypass. It argues that differences between the two modes and a benefit for pulsatile perfusion, are most clearly manifested in identifiable high-risk patient groups.

Blood Circulation↗

Interactions between rat C-reactive protein and adult Hymenolepis diminuta.

Interactions between adult Hymenolepis diminuta and rat C-reactive protein (CRP) were investigated in vivo and in vitro. Using an ELISA technique, serum levels of CRP were monitored in rats infected with 100 cysticercoids. Although infection increased the level of this protein in the early stages of parasitization, the increase was not significant until 35 days post-infection (p.i.). Secondary infections did not enhance the response. When H. diminuta was cultured in the presence of CRP, reduced worm motility and opaque areas were observed and electron microscopical studies revealed shedding of microtriches and lysis of the tegument. Initially, damage was restricted to the strobila which correlated with the regional distribution of phosphorylcholine as visualized using immunofluorescence.

Animals↗

Membrane fluidity on the surface of Hymenolepis diminuta (Cestoda): immunological implications.

Regional differences of Hymenolepis diminuta to immune lysis have been investigated by monitoring surface membrane fluidity utilizing fluorescence recovery after photobleaching (FRAP). Although the surface membrane of the newly excysted stage was completely immobile the molecular fluidity of the strobila membrane of 4-day-old parasites was greater than that associated with the scolex-neck region. Significant differences (P > 0.001) occurred in the mobility of the strobila membrane of 4-day-old H. diminuta from 100-worm infections compared with 7- and 21-day-old parasites and 4-day-old individuals from 10-worm infections. Exposure to 50% normal rat serum and 1 mg/ml rat C reactive protein decreased or eliminated membrane fluidity. The significance of membrane mobility is discussed with reference to resistance to complement-mediated lysis and destrobilation.

Animals↗

High-resolution fluorescence in situ hybridization of human Y-linked genes on released chromatin.

Genes within the differential region of the human Y chromosome do not recombine, and therefore the determination of their location depends on physical mapping. Yeast artificial chromosome (YAC) contigs spanning the euchromatic region of the human Y have become a powerful tool for the generation of an overlapping clone map. With this approach, however, complete physical mapping is difficult in Y euchromatic regions that are rich in repetitive sequences. We have, therefore, made use of the fluorescence in situ hybridization technique as an alternative strategy for physically mapping the PRKY and AMELY genes as well as the TSPY, RBM and DAZ gene families to human Y chromosomes in prometaphase and to extended Y chromatin in interphase. From our results, the following order of gene sequences in interval 3 of the short arm of the human Y chromosome is suggested: TSPY major with few RBM sequences interspersed-PRKY-AMELY-TSPY minor with few RBM sequences interspersed-cen. On the long arm, RBM sequences appear to be distributed over wide regions of intervals 5 and 6 with few TSPY sequences interspersed. Distal to an RBM signal cluster, a large cluster of DAZ signals is located with only a few DAZ and RBM signals overlapping in between the two clusters.

Cell Cycle Proteins↗

Comparative mapping of Xp22 genes in hominoids--evolutionary linear instability of their Y homologues.

Several genes located within or proximal to the human PAR in Xp22 have homologues on the Y chromosome and escape, or partly escape, inactivation. To study the evolution of Xp22 genes and their Y homologues, we applied multicolour fluorescence in situ hybridization (FISH) to comparatively map DNA probes for the genes ANT3, XG, ARSD, ARSE (CDPX), PRK, STS, KAL and AMEL to prometaphase chromosomes of the human species and hominoid apes. We demonstrate that the genes residing proximal to the PAR have a highly conserved order on the higher primate X chromosomes but show considerable rearrangements on the Y chromosomes of hominoids. These rearrangements cannot be traced back to a simple model involving only a single or a few evolutionary events. The linear instability of the Y chromosomes gives some insight into the evolutionary isolation of large parts of the Y chromosomes and thus might reflect the isolated evolutionary history of the primate species over millions of years.

Animals↗