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Biomedical subjects

J M Vogel

Publications and source records attributed to J M Vogel.

At least 37 records · Page 2Linked to original sources
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

Molecular characterization of the C3HfB/HeN H-2Kkm2 mutation. Implications for the molecular basis of alloreactivity.

The C3HfB/HeN (C3Hf) mouse strain expresses an H-2Kk molecule, previously denoted H-2Kkv1, that is structurally and functionally distinct from H-2Kk of the parental C3H strain. By molecular genetic analysis, we demonstrate that the C3Hf H-2K gene carries a homozygous coding region mutation relative to the C3H allele, revealing that C3Hf meets the requirements for assignment of a mutant haplotype, H-2km2. C3Hf H-2Kkm2 bears a single clustered substitution of four nucleotides within 14 contiguous nucleotides in exon 3. Since this sequence also is present intact at the homologous position in H-2Dk of both C3H and C3Hf, the origin of the H-2Kkm2 mutation is consistent with a nonreciprocal sequence transfer from the H-2Dk donor gene, analogous to the mechanism proposed for generation of the H-2Kb mutations. The H-2Kkm2 mutation encodes three clustered amino acid substitutions, at positions 95, 98, and 99, that map to one of the large beta strands at the bottom of the peptide antigen binding cleft of the H-2Kkm2 molecule. The nature and location of these amino acid substitutions are unique relative to any other known H-2 mutant or HLA variant, and underscore the importance of the beta-pleated sheet in influencing CTL recognition. These results indicate that H-2Kkm2 alloantigenicity may derive largely from altered presentation of self cellular peptides.

Amino Acid Sequence↗
PubMed1988

Detection of prefracture spinal osteoporosis using bone mineral absorptiometry.

Bone mineral measurements have been criticized for their inability to clearly distinguish fracture and "nonfracture" populations. However, this failure is not unexpected, since some individuals in the "nonfracture" group have low bone mass and are at increased risk but have not yet experienced fractures. Although standard radiographs are not sensitive indicators of vertebral demineralization, they do identify some of the "prefracture" osteoporotic subpopulation within the nonfracture group. Prospective follow-up of 536 Japanese-American women demonstrated that 14 new spine fractures occurred in the prefracture osteoporosis group, whereas none occurred in the nonosteoporotic group (p less than or equal to 0.03). However, bone mineral content (BMC) measurements using photon absorptiometry were much more accurate than radiographs as indicators of spine fracture risk. BMC values were somewhat higher in the prefracture group than in those with existing fractures, but values for both groups were significantly lower than in nonosteoporotic patients even after adjusting for age, height, and weight (p less than 0.0001). The magnitude of the difference was proportional to the trabecular bone content of the measurement site; the differences were greatest for the os calcis and lumbar spine, smaller for the distal radius, and least for the proximal radius. The prevalence of spinal osteoporosis (including both fracture and prefracture cases) was inversely proportional to BMC (p less than 0.0001). Again, the relations were strongest for the os calcis and lumbar spine. These results indicate that BMC measurements are valid indicators of osteoporosis status, particularly when osteoporosis is defined to include both patients with existing fractures and those at increased risk for fractures. However, dual-photon spine BMC was adversely influenced by the presence of aortic calcification, arthritis, and other disease processes (p less than or equal to 0.0001).

Age Factors↗
PubMed1988

The clinical relevance of calcaneus bone mineral measurements: a review.

The use of bone mineral content (BMC) measurements to assist in the management of osteoporosis has received increasing emphasis in recent years. Although the calcaneus, an essentially trabecular bone (90-95%), has been used extensively in the NASA experiments, few data relating to primary osteoporosis have appeared in the literature until recently. This paper is a review of the methods of measurement, their precision and methods of calibration, and the relationship of calcaneal mineral content to age, height, weight, other bone sites, degree of spinal osteoporosis, metabolic bone disease and the effects of therapeutic drugs. Prospectively, calcaneal BMC relates as well as spinal BMC to osteoporotic fracture risk. It is this use of BMC measurements which has the most promise for the future. The data indicate that osteoporosis is a systemic disease and trabecular bone losses are reflected in the calcaneus as well as in the spine itself.

Absorptiometry, Photon↗
PubMed1988

A model for estimating the potential costs and savings of osteoporosis prevention strategies.

A model was developed which estimates the costs of osteoporosis risk evaluation and treatment, and the resulting savings in terms of reduced fracture frequency, for the adult female population of the United States. In the absence of treatment, the model predicts 1.44 million fractures will occur annually from non-violent causes. Treatment of all women beginning at age 50 with an agent that slows bone loss by 50% would reduce the number of these fractures by 0.59 million. Selective treatment of the 47% of women at the greatest fracture risk would reduce the number of fractures by 0.45 million, but would only cost 47% as much as treating all women. Additional data are required before the model can be used to evaluate specific treatment regimens. However, it appears that selective treatment of those at highest risk would yield the greatest benefit to cost ratio, if only benefits related to reduced fracture frequency are considered.

Age Factors↗
PubMed1988

Precision error in dual-photon absorptiometry related to source age.

An average, variable precision error of up to 6% related to source age was observed for dual-photon absorptiometry of the spine in a longitudinal study of bone mineral content involving 393 women. Application of a software correction for source decay compensated for only a portion of this error. The authors conclude that measurement of bone-loss rates using serial dual-photon bone mineral measurements must be interpreted with caution.

Adult↗
PubMed1987

DNA sequence analysis of the C3H H-2Kk and H-2Dk loci. Evolutionary relationships to H-2 genes from four other mouse strains.

We generated nucleotide sequences for H-2Kk and H-2Dk from the C3H mouse, as well as for a genomic clone of H-2Db, in order to conduct an evolutionary analysis of the H-2 genes from three haplotypes, k, d, and b. H-2Kk from both the C3H and AKR strains, H-2Kd, H-2Kb, H-2Dk, H-2Ld, H-2Dd, H-2Db, and H-2Dp DNA sequences were aligned, and the alignments used to construct phylogenetic trees inferring the evolutionary relationships among the nine genes by two independent methods. Both approaches yielded trees with similar topologies. In addition, the sequence alignments revealed patterns of nucleotide substitutions which implicate both point mutation and recombination in the divergence of the H-2 genes. Future considerations for evolutionary analysis of class I genes are discussed.

Amino Acid Sequence↗
PubMed1987

Definition of a spine fracture threshold based upon prospective fracture risk.

Assessment of fracture threshold (FT) could have important clinical application in determining which individuals should be treated preventively, and what level of therapy to prescribe, if suitable treatment regimens can be developed. We propose that FT be defined as the bone mineral content (BMC) at which the risk of fracture doubles, relative to premenopausal women, as determined by logistic regression analysis of spine fracture incidence in a prospective study of 408 postmenopausal women. The observed values for the FT agree well with those reported by others, based upon more arbitrary definitions. More than 90% of individuals with new nonviolent spine fractures have BMC below the fracture threshold, while fewer than 10% of younger women (age 30-45) are below this value. Although not all women with BMC below the FT have had fractures, they are at increased risk of fracture. Women with BMC equivalent to the FT have at least a 5% chance of fracture over a 10-year period, and the probability of fracture rises rapidly as BMC decreases. BMC appears to be a much stronger predictor of fracture risk than age or body size (height or weight). Thus, use of a BMC fracture threshold to categorize individual risk could provide a more objective basis for clinical decision making.

Adult↗