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P Marshall

Publications and source records attributed to P Marshall.

At least 19 recordsLinked to original sources
PubMed1992

The I-CeuI endonuclease recognizes a sequence of 19 base pairs and preferentially cleaves the coding strand of the Chlamydomonas moewusii chloroplast large subunit rRNA gene.

The I-CeuI endonuclease is a member of the growing family of homing endonucleases that catalyse mobility of group I introns by making a double-strand break at the homing site of these introns in cognate intronless alleles during genetic crosses. In a previous study, we have shown that a short DNA fragment of 26 bp, encompassing the homing site of the fifth intron in the Chlamydomonas eugametos chloroplast large subunit rRNA gene (Ce LSU.5), was sufficient for I-CeuI recognition and cleavage. Here, we report the recognition sequence of the I-CeuI endonuclease, as determined by random mutagenesis of nucleotide positions adjacent to the I-CeuI cleavage site. Single-base substitutions that completely abolish endonuclease activity delimit a 15-bp sequence whereas those that reduce the cleavage rate define a 19-bp sequence that extends from position -7 to position +12 with respect to the Ce LSU.5 intron insertion site. As the other homing endonucleases that have been studied so far, the I-CeuI endonuclease recognizes a non-symmetric degenerate sequence. The top strand of the recognition sequence is preferred for I-CeuI cleavage and the bottom strand most likely determines the rate of double-strand breaks.

Animals↗
PubMed1991

Influx of extracellular calcium is required for the membrane translocation of 5-lipoxygenase and leukotriene synthesis.

Our studies assessed the effects of increases in intracellular calcium concentrations [( Ca2+]i) on leukotriene synthesis and membrane translocation of 5-lipoxygenase (5LO). The calcium ionophore ionomycin and the tumor promoter thapsigargin stimulated leukotriene production and translocation of 5-lipoxygenase to the membrane. Both agents elicited prolonged rises in [Ca2+]i. Leukotriene C4 production associated with [Ca2+]i in cells stimulated with various concentrations of ionomycin and thapsigargin suggests that a threshold [Ca2+]i level of approximately 300-400 nM is required. In the absence of extracellular Ca2+, both the ionomycin- and thapsigargin-induced rises in [Ca2+]i were transient, indicating that the prolonged [Ca2+]i elevation is due to an influx of extracellular Ca2+. Addition of EGTA to the external medium before, or at different times during, the treatment with ionomycin or thapsigargin instantaneously inhibited 5LO translocation and leukotriene synthesis, indicating that Ca2+ influx plays an essential role in 5LO membrane translocation and leukotriene synthesis. No leukotriene production was detected when cells were stimulated by a physiological stimulus of leukotriene D4. The addition of 100 nM leukotriene D4 triggered peak rises in [Ca2+]i that were comparable to those achieved by the ionomycin and thapsigargin. However, the leukotriene D4 induced rise was transient and rapidly declined to a lower but still elevated steady-state level, which was attributed to Ca2+ influx. Stimulation with 100 nM leukotriene D4 for 15 s increased the cellular levels of 1,4,5-inositol triphosphate (IP3), 1,3,4-IP3, and 1,3,4,5-inositol tetraphosphate (IP4).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Cleavage pattern of the homing endonuclease encoded by the fifth intron in the chloroplast large subunit rRNA-encoding gene of Chlamydomonas eugametos.

The fifth group-I intron in the chloroplast large subunit rRNA-encoding gene of Chlamydomonas eugametos (CeLSU.5) is mobile during interspecific crosses between C. eugametos and Chlamydomonas moewusii. Like the six other mobile introns that have been well characterized so far, CeLSU.5 contains a long open reading frame (ceuIR) coding for a site-specific endonuclease (I-CeuI) that cleaves the C. moewusii intronless gene in the vicinity of the intron-insertion site. This stimulates gap repair and mediates efficient transfer of the intron at its cognate site. By expressing the ceuIR gene in the Escherichia coli vectors pKK233-2 and pTRC-99A, we recently demonstrated that the endonuclease is highly toxic to E. coli [Gauthier et al., Curr. Genet. 19 (1991) 43-47]. To eliminate this problem and characterize the cleavage pattern and recognition sequence of the I-CeuI endonuclease, we have expressed the ceuIR gene in E. coli under the control of a bacteriophage T7 promoter in a tightly regulated M13 system, and developed an in vitro system to assay partially purified I-CeuI activity. This allowed us to determine that I-CeuI recognizes a sequence of less than 26 bp centered around the insertion site and produces a staggered cut 5 bp downstream from this site, yielding 4-nucleotide (CTAA), 3'-OH overhangs.

Animals↗
PubMed1991

Analgetic activity of SK&F 105809, a dual inhibitor of arachidonic acid metabolism.

The analgetic activity of inhibitors of 5-lipoxygenase (5-LO) and cyclooxygenase (CO) was investigated using rat Randall-Selitto (RS) hyperalgesia and mouse phenylbenzoquinone (PBQ)-induced abdominal constriction assays. Using the RS assay, the CO inhibitors indomethacin, naproxen, and ibuprofen all effectively reduced hyperalgesia; whereas, the inhibitors of leukotriene production, MK886 and phenidone were inactive. SK&F 105809, a dual inhibitor of 5-LO/CO, significantly reduced hyperalgesia. In the PBQ assay, CO inhibitors were active, SK&F 105809 was nearly as potent as naproxen, and MK886 and phenidone were found to be active. Thus, improved analgetic activity appeared to result from inhibition of 5-LO and CO; whereas, in the RS assay, only CO inhibitors and SK&F 105809 were clearly effective. These results suggest that dual inhibitors, and in particular, SK&F 105809 may be more efficient analgesic agents than selective CO inhibitors in clinical situations in which 5-LO products play a significant role.

Analgesics↗
PubMed1991

Action of peptidoleukotrienes on ion transport in rabbit distal colon in vitro.

Serosal but not mucosal addition of the peptidoleukotrienes, leukotriene (LT) C4 (LTC4), LTD4 and LTE4 transiently (maximal response within 2 min) increased short-circuit current (Isc) and transepithelial conductance across stripped rabbit colonic mucosa mounted in Ussing chambers. All three peptidoleukotrienes elicited their responses in the presence of amiloride (10 microM) and were inhibited by serosal addition of the NaCl cotransport inhibitors bumetanide (100 microM) and furosemide (1 mM). The effects of the peptidoleukotrienes on Isc and transepithelial conductance were concentration-dependent with maximal effects occurring at 10 microM. Half-maximal effects were produced at 30 nM for LTC4, 50 nM for LTD4 and 450 nM for LTE4. The secretory responses to both LTD4 and LTE4 were antagonized in a concentration-dependent manner by the LTD4/LTE4 receptor antagonist, SK&F 104353 (2(S)-hydroxy-3-(R)-[(2-carboxyethyl)thio]-3-[2-(8 phenyloctyl)phenyl]propanoic acid). Complete inhibition of the LTD4 and LTE4 effects were observed at 0.1 microM SK&F 104353 and half-maximal effects were achieved at 0.6 nM SK&F 104353. At 10 microM SK&F 104353 only 50% inhibition of the LTC4-induced increase in Isc was observed. These results suggest the peptidoleukotrienes stimulate colonic Cl- secretion by receptor-mediated mechanisms and that receptors for LTC4 are distinct from those mediating the action of LTD4/LTE4.

Animals↗
PubMed1990

Absence of close linkage between maternal genes for susceptibility to pre-eclampsia/eclampsia and HLA DR beta.

To test the possibility that maternally expressed susceptibility genes for pre-eclampsia/eclampsia are closely linked to the HLA region on chromosome 6 of the human genome, members of ten pedigrees with multiple cases of these disorders were typed for HLA DR beta restriction fragment length polymorphisms by means of TaqI digests. The data were analysed by the LIPED program to calculate lod scores, by several programs to detect potential heterogeneity of recombination fraction between pedigrees, and by the affected-sibling and the affected-pedigree-member methods. The results exclude close linkage. If the putative susceptibility genes lie on chromosome 6 they must lie at least 5 centiMorgans, and probably more, from the HLA DR beta loci. No indication of linkage at higher recombination fractions was found. The main maternally expressed genes affecting susceptibility to pre-eclampsia are not in the HLA region.

Adult↗
PubMed1990

Adrenaline and nocturnal asthma.

OBJECTIVE: To determine whether the nocturnal fall in plasma adrenaline is a cause of nocturnal asthma. DESIGN: Double blind placebo controlled cross-over study. In the first experiment the nocturnal fall in plasma adrenaline at 4 am was corrected in 10 asthmatic subjects with an infusion of adrenaline after parasympathetic blockade with 30 micrograms/kg intravenous atropine. In the second experiment 11 asthmatic subjects showing similar variations in peak expiratory flow rate had the nocturnal fall in plasma adrenaline corrected by infusion before atropine was given. PATIENTS: Asthmatic subjects with a diurnal variation in home peak expiratory flow rate of greater than 20% for at least 75% of the time in the two weeks before the study. MAIN OUTCOME MEASURES: Peak expiratory flow rate and plasma adrenaline. RESULTS: Correction of the nocturnal fall in plasma adrenaline at 4 am to resting 4 pm levels did not alter peak expiratory flow rate either before or after parasympathetic blockade with atropine. CONCLUSION: A nighttime fall in plasma adrenaline is not a cause of nocturnal asthma.

Adult↗
PubMed1990

"Just one more. . .!" A study into the smoking attitudes and behaviour of patients following first myocardial infarction.

A retrospective analysis of smoking behaviour among 43 smokers admitted to a Coronary Care Unit with their first Myocardial Infarction (M.I.) was conducted in order to describe factors which differentiated ex-smokers post M.I. from continued smokers. A multi-factorial questionnaire was devised to measure attitudes, health belief and social support. A significant difference in attitudes was identified. Health beliefs were also identified as a significant variable. In a re-examination of the Health Belief Model, the experience of the M.I. itself proved to be a prime motivator for smoking cessation, whilst emotional symptoms accounted for continued smoking. The implication for health education and the implementation of smoking cessation groups are discussed.

Attitude to Health↗
PubMed1989

Molecular characterization by high resolution isoelectric focusing of the products encoded by the class II region loci of the MHC in humans. II. DP alpha and DP beta gene variants.

To characterize the molecular polymorphism of the DP alpha and DP beta gene products, the HLA-DP molecules expressed by more than 200 cell lines were individually immunoprecipitated by using the mAb B7/21 and their neuraminidase-treated DP alpha and DP beta chains analyzed in IEF gels. These cell lines, most of them from members of 32 families, allowed the definition, by segregation analysis, of the IEF patterns of the DP polypeptide chains encoded by 129 distinct haplotypes. Both DP alpha and DP beta chains display polymorphic IEF-banding patterns. Two DP alpha (A and B) and seven DP beta (A, B, C, D, E, F, and G) IEF variants were characterized. The DP alpha B variant was found in linkage disequilibrium with both DP beta B and DP beta D. Linkage disequilibrium was also encountered with alleles at the DR and DQ loci. Finally, the correlations between the IEF DP alpha and DP beta variants and the primed lymphocyte test-defined HLA-DP specificities were determined by using a panel of 24 primed lymphocyte test-typed cell lines.

Antibodies, Monoclonal↗
PubMed1989

The clinical medical humanities program at Loyola University of Chicago.

The authors emphasize that an effective medical humanities program must be based on clinically oriented training. They then describe in detail such a program at Loyola University of Chicago Medical Center; the program consists of a four-year required curriculum that is clinically reinforced by having the students accompany attending physicians on rounds and is taught by faculty representing a wide range of disciplines in medicine and other fields. The paper offers several guidelines to the person or persons who would organize and direct a clinical medical humanities program, describes obstacles that the Loyola program faced when it was getting started, presents the purpose, focus, and curricular topics of the program, and discusses its future. The authors conclude that the use of the clinically oriented approach will continue to prevail in medical humanities teaching, both at Loyola and in medical humanities programs overall. This approach challenges good teachers to make their best efforts at reconciling their own disciplines with that of medicine; in this process, a new medical humanities discipline emerges that is not so much an application of the humanities to medicine as it is an evocation of humanities themes from the clinical encounter itself.

Chicago↗
PubMed1989

Influence of plasma catecholamines on the lactate threshold during graded exercise.

This investigation examined the relationship among plasma catecholamines, the blood lactate threshold (TLa), and the ventilatory threshold (TVE) in highly trained endurance athletes. Six competitive cyclists and six varsity cross-country runners performed a graded exercise test via two different modalities: treadmill running and bicycle ergometry. Although maximal oxygen consumption (VO2 max) did not differ significantly for the cyclists for treadmill running and cycling (64.6 +/- 1.0 and 63.5 +/- 0.4 ml O2.kg-1-min-1, respectively), both TLa and TVE occurred at a relatively earlier work load during the treadmill run. The opposite was true for the runners as TLa and TVE appeared at an earlier percent of VO2max during cycling compared with treadmill running (60.0 +/- 1.7 vs. 75.0 +/- 4.0%, respectively, TLa). The inflection in plasma epinephrine shifted in an identical manner and occurred simultaneously with that of TLa (r = 0.97) regardless of the testing protocol or training status. Although a high correlation (r = 0.86) existed for the shift in TVE and TLa, this relationship was not as strong as was seen with plasma epinephrine. The results suggest that a causal relationship existed between the inflection in plasma epinephrine and TLa during a graded exercise test. This association was not as strong for TVE and TLa.

Adult↗
PubMed1989

The rehabilitation of overuse foot injuries in athletes and dancers.

Overuse injuries in athletes and dancers provide a challenge to the diagnostic acumen and rehabilitative and preventive skills of the medical community. The challenge is intensified when the primary lesion is located in the foot, whose levers, arches, and pulleys are responsible for absorbing shock, as well as converting a mobile adapter into a rigid lever for propulsion. A thorough knowledge of these active and passive mechanisms is essential for the appropriate and expeditious management of overuse syndromes. Sports and dance medicine health practitioners must also explore and comprehend the kinesiology of the sports and/or dance activity prevalent among their clientele. Furthermore, in order to determine the etiology and make judicious recommendations, clinicians must familiarize themselves with the density and inclines of popular running and dancing surfaces within their referral area. Rehabilitation of the foot requires a multifaceted approach. Physical therapists dealing with these problems need to develop expertise in manual techniques, along with clinical competency in laser, electrical, and thermal modalities. Reduction of predisposing factors is of utmost importance in the successful management of overuse injuries, and often requires greater skill and attention than does the treatment of the primary lesion.

Athletic Injuries↗