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Biomedical subjects

J M Vogel

Publications and source records attributed to J M Vogel.

At least 19 recordsLinked to original sources

The TATA box promoter region of maize Adh1 affects its organ-specific expression.

We have isolated two lineage-related Mutator (Mu3) transposon-induced Adh1 promoter mutants in maize: Adh1-3F1124 carries a duplicated TATA box and its revertant, Adh1-3F1124r17, bears a deleted TATA box. Both alterations lead to unique patterns of organ-specific ADH1 enzyme expression. Enzyme activity in Adh1-3F1124 sporophytic organs (scutellum and roots) is greatly reduced, while activity levels remain normal in the male gametophyte (pollen). Conversely, enzyme activity in Adh1-3F1124r17 roots and scutellum is partially restored, but is concomitantly reduced in pollen. Transcript analysis suggests (i) that the TATA box region of the Adh1 gene influences post-transcriptional processes in the male gametophyte but not in roots and (ii) that organ-specific transcription signals in the promoter are distinct from the previously identified anaerobic environment-specific cis-acting transcription signals. Different organs appear to provide surrogate TATA function in different ways, leading to organ-specific differences in the length of the Adh1 message 5' leader.

Alcohol Dehydrogenase

Relationship between bone mass and rates of bone change at appendicular measurement sites.

The rate of bone change among postmenopausal women may vary depending upon the initial bone mass. Examining this possibility is difficult, however, because of a negative statistical bias that occurs when change is regressed against the initial value of the same variable. In this article, four statistical methods were applied to measure the association between bone mass and the rate of bone change. The study population was Japanese-American women, who were monitored for approximately 5 years. Bone changes were determined for the calcaneus and the distal and proximal radius. The results were consistent across the bone sites but differed between statistical methods. Three of the four methods indicated that the women with the greater bone mass had the greater loss rates. The fourth method did not support this association. Possible reasons for the discordant results are discussed. Using the "best" estimate of the relationship, a gradual convergence of bone mass was projected over time toward the population mean. The convergence occurred because women with higher bone mass had a somewhat faster loss rate than women with lower bone mass. Overall, however, the variation in bone mass between individuals was large compared to the rate of convergence.

Absorptiometry, Photon

Comparison of left anterior oblique, anterior and geometric mean methods for determining gastric emptying times.

The accurate determination of gastric emptying time requires correction or compensation for tissue attenuation. The gold standard for tissue attenuation correction for gastric emptying is the geometric mean of the gastric counts from the anterior and posterior views. For reasons of efficiency, many community hospitals acquire only the anterior projection. This study addressed the hypothesis that, using the left anterior oblique view alone, one can minimize the effect of variation in attenuation as the meal moves from the fundus to the stomach to the more anterior antrum to a degree equal to that of the geometric mean technique. We studied 42 consecutive patients using a standardized 300-g meal labeled with 650 muCi of 99mTc-sulfur colloid. The patients were imaged in the anterior (ANT), posterior (POST) and left anterior oblique (LAO) views every 15 min for 90 min. Linear regressions were obtained using the ANT, LAO and GM data. Cross-correlation of the T1/2 for 35 cases showed an R value for the GM versus LAO of 0.95 and GM versus ANT of 0.84. The p value greater than 0.49, for the paired two-tailed t-test of the LAO and GM methods. The p value for the ANT and GM methods is 0.0058 indicating a significant difference between these methods. The cross-correlation, F-test p and t-test p values support the hypothesis that there is no significant difference between the geometric mean and left anterior oblique gastric emptying times. It is therefore reasonable to substitute the left anterior oblique for routine GET when using a solid meal in patients with normal gastric anatomy, albeit altered physiology.

Adult

Long-term precision of bone loss rate measurements among postmenopausal women.

Repeated measurements of bone mineral content can indicate the rate of bone loss among postmenopausal women. The clinical utility of such loss rate measurements will depend upon the long-term precision of the measurements. We have analyzed the precision of appendicular bone measurements among 495 Japanese-Americans followed for an average of 5.3 years and of both appendicular and axial measurements among 70 clinical trial participants followed for 2 years. Tables were derived from these analyses to quantitate the precision of individual loss rates under varying measurement conditions that might be encountered in clinical practice. The results demonstrate that only unusually rapid loss rates could be identified with confidence within short intervals, such as 1 year or 2. Extending the length of follow-up, however, appreciably improved the measured loss rate precision. In comparisons between bone sites, appendicular sites were determined to achieve a specified precision within the shortest intervals, followed by spine dual photon absorptiometry measurements. Spine quantitative computerized tomography measurements and measurements of hip sites required considerably longer follow-up intervals to achieve comparable precision.

Aged

The clinical application of serial bone mass measurements.

Although the short-term precision of various bone mineral content (BMC) measurements is known, questions about the clinical use of serial BMC measurements remain: how frequently should BMC be measured? When is it appropriate to calculate bone loss rates? How are estimates of loss rate interpreted? This paper discusses both biological and technical sources of uncertainty, and the estimation of confidence limits for measured bone loss rates. For many, possibly most, patients, calculation of bone loss rate may not be necessary; however, repeated measures of BMC can still be useful for re-evaluating fracture risk. Indications for repeating BMC measurements may include low initial BMC (moderate to high fracture risk), anticipation of rapid bone loss (e.g., menopause, estrogen discontinuation), and verification of treatment efficacy.

Bone Density

Age-related changes in bone mass among Japanese-American men.

Bone mass and appendicular bone loss rates were examined in a cohort of Japanese-American men. Across their age range (ages 61 to 82 years) bone mass steadily declined at the proximal and distal radius, and at the calcaneus. The cross-sectional reduction in bone mass was 3.5-6.3% per decade at the various sites. Longitudinal measurements of the same cohort indicated greater losses than suggested by the cross-sectional data, yet still less than 10% per decade. Linear trends of increasing loss rates with aging were significant at the calcaneus, and marginally significant at the radius sites. However, the oldest men in the cohort strongly influenced these trends. Men under age 75 had essentially constant annual rates of bone loss. The most elderly men had both the lowest bone mass and the greatest bone loss rates.

Age Factors

Characteristics of respondents and nonrespondents in a prospective study of osteoporosis.

During 1981-1982, a cohort of elderly Japanese Americans living in Hawaii was recruited for an epidemiologic study of osteoporosis. The male subjects were simultaneously being examined for an epidemiologic study of heart disease. Baseline data collected from both the men and women at a previous heart disease examination were used to compare responders vs nonresponders. The target population for the osteoporosis study consisted of 1685 men and 1594 women. Of these, 1379 men (81.8%) and 1105 women (72.0%) participated in the initial osteoporosis examination. For each sex, nonrespondents were older and had higher systolic blood pressure levels than did the respondents. Male nonresponders had a higher stroke prevalence and more frequent recent use of vasodilator medicine. Female nonresponders had a less frequent history of having ever taken female hormones than did the responders. The responders and nonresponders were reasonably similar in other respects, as indicated by the comparison of more than 40 other variables. This suggests that nonresponse bias is probably not a major influence in exposure-disease associations in this osteoporosis cohort. We believe this is the first published report dealing with nonresponse characteristics in a cohort study of osteoporosis.

Aged

Vertebral dimension differences between Caucasian populations, and between Caucasians and Japanese.

Various criteria have been proposed for using vertebral measurements to identify vertebral fractures. It is known that the normal distributions of vertebral heights and ratios vary with location within the spine. However, very little is known regarding the degree to which differences in these parameters may exist between populations. We report the vertebra-specific distributions of vertebral dimensions and ratios for Japanese-Americans, and compare these values to published data for Caucasians. The mean Japanese vertebral heights were 1 to 2 mm shorter than Caucasians, which may be due in part to the shorter stature of Japanese. However, differences in mean values were also observed between Caucasian populations. Furthermore, anterior/posterior vertebral height ratios differed between Caucasian studies, and between races. Additional studies are needed to determine to what degree these differences are due to technical and biological factors before criteria derived from one population can be used for identifying vertebral fractures in other populations of the same, or different, race.

Adult

Changes in body fluid compartments during a 28-day bed rest.

The extravascular fluid responses to real or simulated space-flight are not well-documented. In this study serial isotope measurements were used to obtain measurements of the body fluid responses of 10 22-29-year-old men during 28 d of simulated microgravity (bed rest). The subjects were maintained on a controlled metabolic diet for 7 d before the study, during 14 d of ambulatory control, 28 d of horizontal bed rest, and 14 d of ambulant recovery. Fluid compartments were measured on control days 1 and 9, bed rest days 2, 14, and 28, and recovery days 7 and 14. By day 2 of bed rest, plasma volume (PV) and extra-cellular volume (ECV) decreased significantly by an average 209 and 533 ml, respectively. Red cell volume (RCV) and total body water (TBW) decreased more slowly, with average losses of 128 and 1,316 ml, respectively, after 28 d of bed rest. Early in the bed rest, TBW loss was mostly from the ECV. Thereafter, the TBW deficit was derived from the intracellular compartment, which decreased an average of 838 ml after 28 d. These results suggest losses from all fluid compartments during bed rest, with no evidence of restoration of ECV after 1-2 weeks.

Adult

A critical review of bone mass and the risk of fractures in osteoporosis.

The usefulness of various bone mineral measurement techniques is a subject of current controversy. In order to explore whether disparate conclusions may have arisen from differences in analytic methodology, data from published reports of bone mass and nonviolent fractures have been reanalyzed in terms of fracture risk. In the large majority of studies, reduced bone mass was associated with an increased risk of fractures. However, the magnitude of the relationship varied much more among cross-sectional studies than among prospective studies, suggesting that bias related to subject selection and/or postfracture bone loss may have strongly influenced the cross-sectional findings. We conclude that more emphasis should be given to the results of prospective studies, and that more attention should be paid to subject selection in all investigations. Analyzing and presenting results in terms of fracture risk would probably reduce the level of confusion in the field and provide more clinically relevant information. These issues are also applicable to studies of potential fracture risk factors other than bone mass, such as bone structure and bone quality.

Aged

Overlapping palindromic sequences associated with somatic deletion and meiotic recombination of MHC class I genes.

H-2L-null variants were immunoselected from a transfected murine fibroblast cell line carrying a single copy H-2L gene, and were characterized to determine the basis for the loss of this MHC class I cell surface product. Molecular analysis indicated that inactivation of H-2L expression in nearly every null clone resulted from an apparent deletion or rearrangement of 5'-flanking and 5'-coding H-2L sequences, with breakpoints consistently mapping to within a 550 bp GC-rich region between exon 1 and the middle of intron 2. Notably, this region of the H-2L gene contains a large number of overlapping, inverted repeat sequences as well as potential topoisomerase I cleavage sites. Examination of several in vivo mutant class I genes, believed to have been generated by recombination, has revealed that each of these genes bears similar palindromic structures overlapping or adjacent to the regions of sequence exchange. These findings suggest that inverted repeat sequences may play a role in recombination and deletion within the MHC class I multigene family.

Animals

Comparison of cross-sectional and longitudinal measurements of age-related changes in bone mineral content.

Age-related, postmenopausal bone loss was examined among a cohort of Japanese-American women living in Hawaii. None of the women were using estrogens or thiazides. Cross-sectional and longitudinal measurements of bone mineral content were compared at the calcaneus, the proximal radius, and the distal radius. Cross-sectional measurements were also available for the lumbar spine. The longitudinal data showed a slowing rate of bone loss with increasing age at the radius sites. By contrast, the cross-sectional data suggested constant rates of bone loss for all ages at both radius sites and the spine. The calcaneus demonstrated a complex pattern of bone loss in both cross-sectional and longitudinal analyses. The loss rates among women in their fifties were greater than for those in their sixties. From the middle sixties onward calcaneal bone loss remained essentially constant. Because of the sustained bone loss, however, women in their seventies were actually losing greater percentages of their calcaneal bone mineral than they had in their sixties.

Aged

Perspectives: methodologic issues in evaluating risk factors for osteoporotic fractures.

Techniques for measuring bone mineral content (BMC) were developed for the purpose of providing an objective and noninvasive indication of bone strength (or lack thereof) and fracture risk, to the extent that strength relates to bone mass. As such, BMC measurements could help to (1) identify those who are most likely to experience nonviolent fractures in the future and who would therefore benefit most from preventive measures, (2) improve their treatment compliance, and (3) monitor the efficacy of treatments intended to reduce bone loss. All these potential uses require that the measurement provide an indication of fracture risk (probability of fractures). During the past 10-15 years there have been conflicting reports regarding the association of reduced BMC with nonviolent fractures. Some authors have criticized the usefulness of BMC measurements, whereas others have questioned the value of one or more techniques. However, the epidemiology of osteoporosis has only recently been subjected to rigorous study. The use of appropriate statistical methods for relating fracture risk to bone mass may be no more widely practiced in osteoporosis epidemiology today than it was for studying risk factors (e.g., blood pressure) in cardiovascular epidemiology during the 1960s. The intent of this article is to explore three areas that may have contributed to controversy in the study of bone mass and fracture occurrence: (1) perspective of the investigators, (2) study design, and (3) analytic methodology. Although the focus of this paper is on bone mass, these considerations are equally applicable to some investigations of other risk factors for osteoporotic fractures (e.g., bone architecture, bone turnover and loss rate, or biochemical markers of bone loss).

Bone Density

A novel H-2K splice form: predictions for other alternative H-2 splicing events.

A large number of H-2K and H-2D cDNA clones from a C3HfB/HeN spleen cDNA library were extensively characterized. All H-2Dk cDNAs were shown to exhibit the short form of exon 8, consistent with the presence of a single lariat branchpoint site within intron 7. Twenty-five H-2Kkm2 cDNAs were found to bear a short exon 8, whereas only two clones were shown to carry the longer form of this exon. In one of the H-2Kkm2 cDNAs, a novel pattern of H-2 splicing was identified, in which an extra 15 nucleotides, derived from the 3' end of intron 5, were inserted between the intact and unaltered exon 5 and exon 6 sequences. Resulting from the apparent use of a cryptic splice acceptor site in place of the canonical intron 5 site, this insertion is predicted to generate an in-frame insertion of five nonpolar amino acid residues within a highly polar region of the intracytoplasmic domain of the H-2K polypeptide. The features of this novel splice form served as the basis for predicting additional rare, alternative H-2 pre-mRNA splicing events that might produce functionally relevant microheterogeneity in the encoded H-2 gene products.

Animals

Methodological issues in comparing genetic and environmental influences on bone mass.

Measurements of bone mineral content (BMC), bone width (BW) and BMC/BW (BMA) at the proximal radius were compared for both Japanese and Japanese-American men and women, after adjusting for measurement technique differences. Within each nationality, men had greater values than women at all ages. Japanese-Americans had substantially greater values of BMC (6-10%) and BMA (16-17%), but lower BW (-12 to -15%), relative to Japanese. Adjustment for body size (height and weight) reduced the magnitude of these differences by approximately one-half for BMC, but had a smaller effect on BMA, and slightly increased the difference in BW. Comparison of these results to published data suggests that environmental factors may have influences on bone mass that are similar in magnitude to the effects of race. The need for additional studies to address potential methodological problems is discussed, using this and other reports as examples.

Adult

A comparison of single and multi-site BMC measurements for assessment of spine fracture probability.

In a prospective study of 699 women, 39 new spine fracture cases were observed during a mean follow-up of 3.6 yr. Spine fracture incidence was compared to initial bone mineral content (BMC) of the calcaneus, distal radius, proximal radius, and the lumbar spine. BMC at all four sites was significantly related to spine fracture incidence. Women at -1 s.d. for calcaneal BMC had a sevenfold greater probability of spine fracture than women at +1 s.d.; women at -2 s.d. had a 50-fold greater probability than women at +2 s.d., even after adjustment for the effects of age. Combinations of BMC at two sites further strengthened the relationship to spine fracture; the best two-site combination is calcaneus and distal radius BMC. Thus women can be categorized and stratified according to future fracture risk, and the selection of postmenopausal women for preventive treatments can be guided by measurements of BMC.

Adult