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Biomedical subjects

A Morrison

Publications and source records attributed to A Morrison.

At least 55 records · Page 3Linked to original sources
PubMed1996

A comparison of variable-dose patient-controlled analgesia with fixed-dose patient-controlled analgesia.

We examined the effect on the quality of analgesia and side effects of increasing the patient control component of morphine patient-controlled analgesia (PCA) by offering the patient a choice of bolus dose sizes. Using a three-button hand piece, patients could choose between 0.5-, 1.0-, and 1.5-mg boluses of morphine (variable-dose PCA, VDPCA). Successful demands were delivered by a modified Graseby 3400 Anaesthesia Pump controlled by a Toshiba T1900 computer. This system was compared with conventional fixed-dose PCA (FDPCA) (1.0 mg of morphine) delivered by a Graseby 3300 PCA Pump. Both treatment groups had a 5-min lockout interval. Sixty patients were randomly assigned to receive either VDPCA or FDPCA after major abdominal gynecological surgery or hip or knee arthroplasty. Treatment groups did not differ in their duration of PCA therapy, total morphine consumption, or time spent with mild or severe oxyhemoglobin desaturation. There were no differences in their ease of controlling pain, satisfaction with pain control, experience of pain on movement, quality of sleep, severity of nausea, or incidence of vomiting. Although the more complex VDPCA technique provides adequate postoperative analgesia, it does not offer any advantage over conventional FDPCA.

Adult↗
PubMed1996

Paralogous Hox genes: function and regulation.

The Hox homeobox gene family plays a pivotal role in regulating patterning and axial morphogenesis in vertebrates. Molecular characterization of the four Hox clusters has shown that they are evolutionarily related with respect to sequence, organization, and expression, suggesting they arose by duplication and divergence. Transgenic analysis has clearly demonstrated the functional roles of individual genes in a broad range of embryonic tissues, and in compound mutants has addressed the issues of cooperativity and redundancy. There is an emerging picture of the cis-regulatory elements underlying Hox expression, and for the 3' members of the clusters there is a considerable degree of conservation between paralogous genes with respect to their functional roles and regulatory control.

Animals↗
PubMed1996

In vitro and transgenic analysis of a human HOXD4 retinoid-responsive enhancer.

Expression of vertebrate Hox genes is regulated by retinoids in cell culture and in early embryonic development. We have identified a 185-bp retinoid-responsive transcriptional enhancer 5' of the human HOXD4 gene, which regulates inducibility of the gene in embryonal carcinoma cells through a pattern of DNA-protein interaction on at least two distinct elements. One of these elements contains a direct repeat mediating ligand-dependent interaction with retinoic acid receptors, and is necessary though not sufficient for the enhancer function. The HOXD4 enhancer directs expression of a lacZ reporter gene in the neural tube of transgenic mouse embryos in a time-regulated and regionally restricted fashion, reproducing part of the anterior neuroectodermal expression pattern of the endogenous Hoxd-4 gene. Administration of retinoic acid to developing embryos causes alterations in the spatial restriction of the transgene expression domain, indicating that the HOXD4 enhancer is also a retinoid-responsive element in vivo. The timing of the retinoic acid response differs from that seen with more 3' Hox genes, in that it occurs much later. This shows that the temporal window of competence in the ability to respond to retinoic acid differs between Hox genes and can be linked to specific enhancers. Mutations in the direct repeat or in a second element in the enhancer affect both retinoid response in culture and developmental regulation in embryos, suggesting that co-operative interactions between different factors mediate the enhancer activity. These data provide further support for a role of endogenous retinoids in regulation and spatial restriction of Hox gene expression in the central nervous system.

Animals↗
PubMed1996

Retinoids and Hox genes.

The vertebrate embryonic body plan is constructed through the interaction of many developmentally regulated genes that supply cells with the essential positional and functional information they require to migrate to their appropriate destination and generate the proper structures. Some molecular cues involved in patterning the central nervous system, particularly in the hindbrain, are interpreted by the Hox homeobox genes. Retinoids can affect the expression of Hox genes in cells lines and embryonic tissues; the hindbrain and branchial region of the head are particularly sensitive to the teratogenic effects of retinoic acid. The presence of endogenous retinoic acid, together with the distribution of retinoid binding proteins and nuclear receptors in the developing embryo, strongly suggest that retinoic acid is a natural morphogen in vertebrate development. The molecular basis for the interaction between retinoic acid and the Hox genes has been aided in part by approaches using deletion analysis in transgenic mice carrying lacZ reporter constructs. Such studies have identified functional retinoic acid response elements within flanking sequences of some of the most 3' Hox genes, suggesting a direct interaction between the genes and retinoic acid. Furthermore, as demonstrated using transgenic mice carrying Hoxb-1/lacZ constructs, multiple retinoic acid response elements may cooperate with positive and negative regulatory enhancers to specify pattern formation in the vertebrate embryo. These types of studies strongly support the normal roles of retinoids in patterning vertebrate embryogenesis through the Hox genes.

Animals↗
PubMed1995

Detecting conserved regulatory elements with the model genome of the Japanese puffer fish, Fugu rubripes.

Comparative vertebrate genome sequencing offers a powerful method for detecting conserved regulatory sequences. We propose that the compact genome of the teleost Fugu rubripes is well suited for this purpose. The evolutionary distance of teleosts from other vertebrates offers the maximum stringency for such evolutionary comparisons. To illustrate the comparative genome approach for F. rubripes, we use sequence comparisons between mouse and Fugu Hoxb-4 noncoding regions to identify conserved sequence blocks. We have used two approaches to test the function of these conserved blocks. In the first, homologous sequences were deleted from a mouse enhancer, resulting in a tissue-specific loss of activity when assayed in transgenic mice. In the second approach, Fugu DNA sequences showing homology to mouse sequences were tested for enhancer activity in transgenic mice. This strategy identified a neural element that mediates a subset of Hoxb-4 expression that is conserved between mammals and teleosts. The comparison of noncoding vertebrate sequences with those of Fugu, coupled to a transgenic bioassay, represents a general approach suitable for many genome projects.

Animals↗
PubMed1995

Comparative analysis of chicken Hoxb-4 regulation in transgenic mice.

We cloned the chicken Hoxb-4 gene and performed in situ analysis to investigate conservation in patterns of expression between the chicken and mouse. The anterior boundaries of expression for both genes in segmented tissues, such as the hindbrain and paraxial mesoderm, map to the same rhombomere (r) (r6/r7) and somite (s) (s6/s7) limits, showing a direct correlation between expression of a specific Hox gene and patterning identical axial structures in both species. Given this similarity in expression we have tested the functional activity of cis-regulatory regions from the chicken Hoxb-4 gene in transgenic mice to identify and map components conserved between the species. We identified enhancers which contain conserved blocks of sequence identity and which are necessary to mediate mesodermal and neural restricted patterns of expression. However, only the neural enhancer directs the proper anterior boundary of expression (r6/r7), indicating that only a subset of the underlying molecular components regulating Hoxb-4 expression are functionally conserved between species.

Animals↗
PubMed1995

The drug-of-choice phenomenon psychological differences among drug users who preferred different drugs.

The Eysenck Personality Questionnaire, the Sensation Seeking Scale, and the Brief Symptom Inventory were administered to 125 recovering drug users with three or more months abstinent from drugs. Subjects were divided according to drug preference: opiates, stimulants, marijuana, alcohol, and a polydrug preference. Opiate users were significantly higher in Susceptibility to Boredom. Alcohol misusers compared to a combined stimulant, opiate, and polydrug group were significantly lower in Extroversion and Susceptibility to Boredom. Subjects raised in drug/alcohol-using families scored significantly higher on Neuroticism and on the Positive Symptom Total of the BSI, and had a higher rate of suicidality.

Adolescent↗
PubMed1994

Disruption of the gene encoding the EcmA, extracellular matrix protein of Dictyostelium alters slug morphology.

The ecmA and ecmB genes of Dictyostelium are expressed in prestalk and stalk cells. They encode components of the slime sheath, the extracellular matrix that surrounds the migrating slug, and the stalk tube, the matrix that encases stalk cells. We have generated, by homologous gene disruption, a mutant in which the ecmB gene is inactivated but the strain develops normally. In contrast, ecmA null mutant strains develop to form abnormally long and thin standing slugs. While the slime sheath of mutant slugs appears to be normal in electron microscopic observations, the sheath material remaining on the substratum after the slug travels through it is abnormally susceptible to breakage. After a short period of migration the axial ratio of mutant slugs decreases to that of normal slugs and, at culmination, normal fruiting bodies are produced. These data suggest that the EcmA protein has its primary role during slug formation, where it contributes to the strength of the slime sheath, and that the function of the EcmB protein is dispensible.

Animals↗
PubMed1994

The 3'-->5' exonucleases of both DNA polymerases delta and epsilon participate in correcting errors of DNA replication in Saccharomyces cerevisiae.

DNA polymerases II (epsilon) and III (delta) are the only nuclear DNA polymerases known to possess an intrinsic 3'-->5' exonuclease in Saccharomyces cerevisiae. We have investigated the spontaneous mutator phenotypes of DNA polymerase delta and epsilon 3'-->5' exonuclease-deficient mutants, pol3-01 and pol2-4, respectively. pol3-01 and pol2-4 increased spontaneous mutation rates by factors of the order of 10(2) and 10(1), respectively, measured as URA3 forward mutation and his7-2 reversion. Surprisingly, a double mutant pol2-4 pol3-01 haploid was inviable. This was probably due to accumulation of unedited errors, since a pol2-4/pol2-4 pol3-01/pol3-01 diploid was viable, with the spontaneous his7-2 reversion rate increased by about 2 x 10(3)-fold. Analysis of mutation rates of double mutants indicated that the 3'-->5' exonucleases of DNA polymerases delta and epsilon can act competitively and that, like the 3'-->5' exonuclease of DNA polymerase delta, the 3'-->5' exonuclease of DNA polymerase epsilon acts in series with the PMS1 mismatch correction system. Mutational spectra at a URA3 gene placed in both orientations near to a defined replication origin provided evidence that the 3'-->5' exonucleases of DNA polymerases delta and epsilon act on opposite DNA strands, but were in sufficient to distinguish conclusively between different models of DNA replication.

Amino Acid Sequence↗
PubMed1994

Elderly women in northern New England exhibit seasonal changes in bone mineral density and calciotropic hormones.

A seasonal component to bone loss has been reported in some postmenopausal women. We hypothesized that elderly women in northern New England would be at high risk for bone loss during winter because of their age, diet and lack of sunlight. Eighteen elderly but healthy women (mean age 77 years) started a 2-year observational study in a remote area of northwestern Maine (Greenville: 45.5 degrees N latitude). Fifteen women completed the study. Bone mineral density of the spine (L-BMD) and hip (F-BMD) and biochemical markers of bone turnover were measured biannually. In vitro photo-conversion of provitamin D3 to previtamin D3 was determined in the winter and spring. Initial calcium and vitamin D intake averaged 700 +/- 72 mg/day and 6.2 +/- 1.2 micrograms/day, respectively. During the first year L-BMD dropped 4.2% (P = 0.002) while F-BMD dropped 2.4% (P = 0.09), primarily because of steep declines during the fall and winter (August to February: L-BMD: 3.6%, P = 0.001; F-BMD: 3.0%, P = 0.04). In that 6-month period, serum 25 hydroxyvitamin D (25(OH)D) fell 13 +/- 6% (P = 0.06) and PTH rose 27 +/- 11% (P = 0.01). Additionally, there was no detectable in vitro conversion of provitamin D to previtamin D over 8 h of one sunny winter day. In the summer, PTH and 25(OH)D reverted to basal levels and significant in vitro photoconversion of provitamin D to previtamin D was detected. In the 2nd year of the study, vitamin D consumption increased (+2.0 +/- 1.2 micrograms/day, P = 0.03 vs. baseline), L-BMD increased slightly (+1.8%, P = 0.05) and F-BMD did not change (+0.5%, P = NS). Again, changes in BMD and vitamin D were seasonal: L-BMD and F-BMD were constant during fall and winter but both sites showed increases during summer (L-BMD: +1.7%, P = 0.04, F-BMD: +1.6%, P = 0.25). In the second winter, serum 25(OH)D fell nearly 20% and PTH rose 17%. Increased dietary consumption of vitamin D was positively correlated with changes in F-BMD at 18 months (r = 0.61, P = 0.02) and resulted in slightly greater serum 25(OH)D concentrations during the second winter than the first. The difference in serum 25(OH)D between the first and second winter was the strongest predictor of lumbar bone accretion during the second year of the study (r = 0.59, P = 0.04). In this 24-month observational study, significant seasonal changes in BMD, 25(OH)D and PTH were reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Tamoxifen and estrogen lower circulating lipoprotein(a) concentrations in healthy postmenopausal women.

Data in the literature suggest that circulating levels of lipoprotein(a) [Lp(a)] and insulinlike growth factor I (IGF-I) respond similarly to therapy with growth hormone, estrogen, or tamoxifen. To more clearly document these relations, we designed a randomized, double-blind, placebo-controlled study of the effects of tamoxifen and continuous estrogen on circulating levels of Lp(a), IGF-I, and IGF binding protein 3 (IGFBP-3) in healthy postmenopausal women. Both estrogen and tamoxifen decreased serum levels of IGF-I to 30% below baseline during the 3 months of treatment, while IGFBP-3 levels were unchanged. Plasma Lp(a) levels decreased to 24% below baseline after 1 month of treatment with either estrogen or tamoxifen (P < .05 for estrogen only); after 3 months Lp(a) decreased to 34% below baseline with tamoxifen therapy (P < .05) but returned to only 16% below baseline with estrogen. The correlation between Lp(a) and IGF-I was highly significant (P < .0001). We conclude that (1) tamoxifen lowers plasma Lp(a) levels in healthy postmenopausal women, (2) the suppressive effects of tamoxifen and estrogen on circulating Lp(a) concentration diverge after the first month of therapy, and (3) circulating levels of Lp(a) and IGF-I are strongly correlated with each other, an indication that they may share regulatory influences.

Aged↗
PubMed1993

Pathway correcting DNA replication errors in Saccharomyces cerevisiae.

Mutation of predicted 3'-->5' exonuclease active site residues of Saccharomyces cerevisiae POL3 DNA polymerase (delta) or deletion of the PMS1 mismatch repair gene lead to relative (to wild type) spontaneous mutation rates of approximately 130 and 41, respectively, measured at a URA3 reporter gene inserted near to a defined replication origin. The POL3 exonuclease-deficient mutant pol3-01 generated most classes of single base mutation in URA3, indicating a broad specificity that generally corresponds to that of the PMS1 system. pol3-01 pms1 haploid cells ceased growth after a few divisions with no unique terminal cell morphology. A pol3-01/pol3-01 pms1/pms1 diploid was viable and displayed an estimated URA3 relative mutation rate of 2 x 10(4), which we calculate to be catastrophically high in a haploid. The relationship between the relative mutation rates of pol3-01 and pms1 was multiplicative, indicating action in series. The PMS1 transcript showed the same cell cycle periodicity as those of a set of DNA replication genes that includes POL3, suggesting PMS1 is co-regulated with these genes. We propose that the POL3 3'-->5' exonuclease and the PMS1 mismatch repair system act on a common pathway analogous to the dnaQ-->mutHLS pathway of DNA replication error correction in Escherichia coli.

Amino Acid Sequence↗