Search PubMed⌕ Search

Biomedical subjects

A Morrison

Publications and source records attributed to A Morrison.

At least 73 records · Page 4Linked to original sources

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↗

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↗

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↗

DNA polymerase II, the probable homolog of mammalian DNA polymerase epsilon, replicates chromosomal DNA in the yeast Saccharomyces cerevisiae.

Two temperature-sensitive DNA polymerase II mutants (pol2-9 and pol2-18) of the yeast Saccharomyces cerevisiae were isolated by the plasmid shuffling method. DNA polymerase II activity partially purified from both mutants was thermolabile, while DNA polymerase I and III activities remained thermotolerant. At the restrictive temperature, the pol2 mutants were defective in chromosomal DNA replication and exhibited the dumbbell terminal morphology typical of DNA replication mutants. The POL2 transcript accumulated periodically during the cell cycle, peaking at the G1/S boundary in the same manner as the transcripts of more than 10 other DNA replication genes. These results indicate that DNA polymerase II participates in nuclear DNA replication. The similarities in structure and activities between the DNA polymerases of yeast and mammals make it likely that mammalian DNA polymerase epsilon too is required for chromosomal DNA replication.

Amino Acid Sequence↗

A simple method of generating axenic derivatives of Dictyostelium strains.

We describe a generally applicable method of adapting Dictyostelium from growth on a bacterial food source to axenic growth. Cells are initially selected by growth on a plastic substratum but subsequently acquire the ability to grow in suspension culture. These strains can be transformed efficiently by DNA-mediated gene transfer.

Animals↗

The incidence of total hip replacement in orthognathic surgery patients receiving short-term steroid therapy.

It is well known that long-term corticosteroid therapy can lead to avascular necrosis of the femoral head. There is suspicion among orthopedic surgeons that short-term, high-dose steroid use poses similar risks. The records of 2,773 patients (1,497 who had total hip replacement and 1,276 who had orthognathic surgery) were retrospectively reviewed. No hip replacements had been done in the orthognathic surgery group and none of the patients in the total hip replacement group had undergone orthognathic surgery. The use of short-course, systemic corticosteroids to reduce postoperative swelling in orthognathic surgery did not seem to cause avascular necrosis of the femoral head.

Adrenal Cortex Hormones↗

Ataxia-telangiectasia: linkage analysis of chromosome 11q22-23 markers in Turkish families.

To further pinpoint the location of the genes for ataxia-telangiectasia on the long arm of chromosome 11, we performed linkage analysis and analysis of recombinants of genetic haplotypes on 14 Turkish families with ataxia-telangiectasia, 12 of which were consanguineous. These studies used more than 25 polymorphic genetic markers spanning a region of the long arm of chromosome 11 that is larger than 50 cM. Seven markers gave significant LOD scores to AT: CJ5, DRD2, CJ208, S144, CD3E, PBGD, and S147, as did haplotypes created with pairs of markers DRD2/CJ5 and S144/CJ208, giving recombination fractions (theta) of 0.00, 0.00, 0.05, 0.08, 0.03, 0.09, 0.07, 0.00, and 0.06, respectively. Monte Carlo analysis of these 14 Turkish families indicated the best location for a single AT gene to be within a 6 cM sex-averaged (3 cM male-specific) interval defined by STMY and CJ77; this was three times more likely than the next most likely location (peak III) at the DRD2 locus. The analysis also revealed a peak (peak II) between S147 and S133, which may represent the complementation group D gene. Recombinant analysis of haplotypes also localized an AT locus to the STMY-CJ77 interval. Taken together, these results suggest that at least two distinct AT loci exist (ATA and ATD) at 11q22-23, with perhaps a third locus, ATC, located very near to the ATA gene. This genetic heterogeneity further complicates plans to isolate the major ATA and ATC genes and to begin identifying AT carriers in the general population.

Ataxia Telangiectasia↗

Attenuating the hypertensive response to laryngoscopy and endotracheal intubation using awake fibreoptic intubation.

Blood pressure and pulse rate measurements were recorded in 35 patients undergoing endotracheal intubation during general anaesthesia (Group A), and 35 patients who had an awake fibreoptic intubation under local anaesthesia (Group B). The mean arterial pressure in Group A rose by a mean of 35 mmHg immediately after intubation, compared with a mean fall of 9 mmHg in Group B. The mean pulse rate in Group A rose by 24 beats per minute (b.p.m.) immediately after intubation, compared with a rise of 3 b.p.m. in Group B. Both these differences were statistically significant (P less than 0.0001 and P less than 0.001 respectively, Mann Whitney U test). Postoperative discomfort was assessed 24 h later by means of linear analogue scales. There was a statistically higher mean score in relation to nose discomfort in Group B (P less than 0.002). Awake fibreoptic intubation successfully reduces the pressor response to endotracheal intubation in normotensive adults. It is suitable for use in those patients who are at risk from the pressor response.

Anesthesia, General↗

Larval population dynamics in a community of nearctic Aedes inhabiting a temporary vernal pool.

The spatial distribution and preadult mortality patterns of 4 cohabiting species of Aedes mosquitoes were studied in a temporary vernal pool at Mt. Carmel, CT, from March to May 1990. The dominant species was Ae. stimulans (79.9%), followed by Ae. canadensis (10.7%), Ae. excrucians (7.5%) and Ae. cinereus (1.9%). First instar larvae of all species aggregated at the edge of the pool and then dispersed to deeper regions as they matured. Larval mortality was high, and the majority occurred during the first stadium (80.9% for Ae. canadensis, 88.9% for Ae. excrucians, 89.1% for Ae. stimulans and 90.0% for Ae. cinereus). A predatory chaobrid, Mochlonyx cinctipes, was implicated as the major mortality factor affecting larval populations.

Aedes↗

Eukaryotic DNA polymerase amino acid sequence required for 3'----5' exonuclease activity.

We have identified an amino-proximal sequence motif, Phe-Asp-Ile-Glu-Thr, in Saccharomyces cerevisiae DNA polymerase II that is almost identical to a sequence comprising part of the 3'----5' exonuclease active site of Escherichia coli DNA polymerase I. Similar motifs were identified by amino acid sequence alignment in related, aphidicolin-sensitive DNA polymerases possessing 3'----5' proofreading exonuclease activity. Substitution of Ala for the Asp and Glu residues in the motif reduced the exonuclease activity of partially purified DNA polymerase II at least 100-fold while preserving the polymerase activity. Yeast strains expressing the exonuclease-deficient DNA polymerase II had on average about a 22-fold increase in spontaneous mutation rate, consistent with a presumed proofreading role in vivo. In multiple amino acid sequence alignments of this and two other conserved motifs described previously, five residues of the 3'----5' exonuclease active site of E. coli DNA polymerase I appeared to be invariant in aphidicolin-sensitive DNA polymerases known to possess 3'----5' proofreading exonuclease activity. None of these residues, however, appeared to be identifiable in the catalytic subunits of human, yeast, or Drosophila alpha DNA polymerases.

Amino Acid Sequence↗

Cloning DPB3, the gene encoding the third subunit of DNA polymerase II of Saccharomyces cerevisiae.

DNA polymerase II purified from Saccharomyces cerevisiae contains polypeptides with apparent molecular masses of greater than 200, 80, 34, 30 and 29 kDa, the two largest of which (subunits A and B) are encoded by the essential genes POL2 and DPB2. By probing a lambda gt11 expression library of yeast DNA with antiserum against DNA polymerase II, we isolated a single gene, DPB3, that encodes both the 34- and 30-kDa polypeptides (subunit C and C'). The nucleotide sequence of DPB3 contained an open reading frame encoding a 23-kDa protein, significantly smaller than the observed molecular masses, 34- or 30-kDa, which might represent post-translationally modified forms of the DPB3 product. The predicted amino acid sequence contained a possible NTP-binding motif and a glutamate-rich region. NTP-binding motif and a glutamate-rich region. A dpb3 deletion mutant (dpb3 delta) was viable and yielded a DNA polymerase II lacking the 34- and 30-kDa polypeptides. dpb3 delta strains exhibited an increased spontaneous mutation rate, suggesting that the DPB3 product is required to maintain fidelity of chromosomal replication. Since a fifth, 29-kDa polypeptide was present in DNA polymerase II preparations from wild-type cell extracts throughout purification, the subunit composition appears to be A, B, C (or C and C') and D. The 5' nontranscribed region of DPB3 contained the MulI-related sequence ACGCGA, while the 0.9-kb DPB3 transcript accumulated periodically during the cell cycle and peaked at the G1/S boundary. The level of DPB3 transcript thus appears to be under the same cell cycle control as those of POL2, DPB2 and other DNA replication genes. DPB3 was mapped to chromosome II, 30 cM distal to his7.

Amino Acid Sequence↗