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Biomedical subjects

M L Johnson

Publications and source records attributed to M L Johnson.

At least 73 records · Page 4Linked to original sources
PubMed1997

Bone dimensional change with age: interactions of genetic, hormonal, and body size variables.

Changes in bony dimensions with age were assessed longitudinally from standardized X-ray films in 170 middle-aged Caucasian women, starting at age 40 years and with a median duration of observation of 21.125 years. Consistent with earlier work, cortical area of the metacarpals and radial shaft declined with age at rates ranging from 0.57 to 0.86%/year. As predicted, estrogen replacement therapy decreased this loss in a dose-dependent manner. Not previously reported is the fact that weight gain over the period of observation reduced upper extremity bone loss. Moreover, this protection was independent of the estrogen effect. In contrast with bone loss in the upper extremity, both femur shaft diameter and femur shaft cortical area increased significantly with age (0.23 and 0.26%/year, respectively). Estrogen replacement therapy inhibited femur shaft expansion but had no effect on femur cortical area. Weight change, however, strongly influenced gain (or loss) of femur cortical area: those in the highest weight change tertile gained 4 times as much cortical area as those in the lowest weight change tertile. VDR genotype also significantly influenced femoral shaft changes: women with the bb genotype had both greater shaft expansion and a greater increase in cortical area. The VDR effects were independent of the effects of weight change and estrogen. Femoral shaft expansion was of sufficient magnitude to suggest that the mechanical properties of the entire femur may change appreciably with age. Finally, contrary to widespread belief, there was significant, if modest, expansion at the femoral neck with age.

Adult↗
PubMed1997

Age-related changes in serum immunoglobulins in patients with familial IgA deficiency and common variable immunodeficiency (CVID).

The concentration of serum immunoglobulins in individuals with IgA deficiency (IgAD) and CVID can vary with age to have practical implications for evaluation, therapy, and genetic analysis. Most IgAD and CVID patients in our clinic population in the Southeastern United States have inherited part or all of two extended MHC haplotypes, referred to as haplotype 1 (HLA-DQB1 0201, HLA-DR3, C4B-Sf, C4A-0, G1-15, Bf-0.4, C2-a, HSP-7.5, TNF alpha-5, HLA-B8, HLA-A1) and haplotype 2 (HLA-DQB1 0201, HLA-DR-7, C4B-S, C4A-L, G11-4.5, Bf-0.6, C2-b, HSP-9, TNF alpha-9, HLA-B44, HLA-A29). In the present study, the clinic records of 68 CVID patients and 73 IgAD patients were reviewed to determine whether patients with familial or MHC-associated IgAD or CVID experience changes in serum immunoglobulin concentrations. An increase in serum immunoglobulin to the normal range was associated with clinical improvement in one patient with CVID and haplotype 2, two patients with IgAD and haplotype 2, and one IgAD patient whose haplotype was not determined. Two patients with haplotype 1 and one with haplotype 2 had a significant decline in serum immunoglobulin: one progressed from normal to IgAD associated with IgG subclass deficiencies, and two progressed from IgAD to CVID. Five of the seven patients with notable changing serum immunoglobulin levels have a family member with either IgAD or CVID. The findings suggest that familial, MHC-associated IgAD and CVID may be either progressive or reversible disorders, and emphasize the value of monitoring immunoglobulin levels in affected individuals and their family members.

Adolescent↗
PubMed1997

Linkage of a gene causing high bone mass to human chromosome 11 (11q12-13)

The purpose of this paper is to report the linkage of a genetic locus (designated "HBM") in the human genome to a phenotype of very high spinal bone density, using a single extended pedigree. We measured spinal bone-mineral density, spinal Z(BMD), and collected blood from 22 members of this kindred. DNA was genotyped on an Applied Biosystems model 377 (ABI PRISM Linkage Mapping Sets; Perkin Elmer Applied Biosystems), by use of fluorescence-based marker sets that included 345 markers. Both two-point and multipoint linkage analyses were performed, by use of affected/unaffected and quantitative-trait models. Spinal Z(BMD) for affected individuals (N = 12) of the kindred was 5.54 +/- 1.40; and for unaffected individuals (N = 16) it was 0.41 +/- 0.81. The trait was present in affected individuals 18-86 years of age, suggesting that HBM influences peak bone mass. The only region of linkage was to a series of markers on chromosome 11 (11q12-13). The highest LOD score (5.21) obtained in two-point analysis, when a quantitative-trait model was used, was at D11S987. Multipoint analysis using a quantitative-trait model confirmed the linkage, with a LOD score of 5.74 near marker D11S987. HBM demonstrates the utility of spinal Z(BMD) as a quantitative bone phenotype that can be used for linkage analysis. Osteoporosis pseudoglioma syndrome also has been mapped to this region of chromosome 11. Identification of the causal gene for both traits will be required for determination of whether a single gene with different alleles that determine a wide range of peak bone densities exists in this region.

Absorptiometry, Photon↗
PubMed1997

Evaluation of protein and energy quality of rendered spent hen meals.

This study evaluated three spent hen meals (SHM) that were produced in commercial rendering plants. The levels (percentage) of selected nutrients (mean and range) in the meals were: CP, 64 (56 to 71); ash, 16 (12 to 18); lysine, 4.0 (3.6 to 4.3); methionine, 1.3 (1.2 to 1.4); cystine, 1.1 (0.8 to 1.5). Protein efficiency ratios (PER; weight gain per unit of protein intake) were determined in chicks fed 10% CP diets containing a SHM as the only source of dietary protein. The PER values for the SHM averaged 1.6 but varied from 1.1 to 2.2. An experiment was conducted using New Hampshire x Columbian chicks during the 7 to 20 d age period to determine the effect of substitution with either 7.5 or 15% of a SHM to a 21.5% CP corn-soybean meal diet. When substituted at 7.5%, growth performance was not affected by two of the SHM but was depressed by the other one. Growth performance was decreased by all SHM when substituted at 15% of the diet. True amino acid digestibility and TMEn of the SHM were determined using the precision-fed cecectomized rooster assay in which four roosters were crop-intubated with 30 g of a SHM and excreta were collected for 48 h. True amino acid digestibility varied among SHM (P < or = 0.05) and digestibility of cystine was substantially lower than digestibility of the other amino acids. Mean TMEn (kilocalories per gram of DM) of the SHM was 3.003 but varied by 44% among samples. The results of this study indicated that SHM has substantial nutritional value for poultry but the nutritional quality may vary greatly among samples.

Aging↗
PubMed1997

Effects of raw material source, ash content, and assay length on protein efficiency ratio and net protein ratio values for animal protein meals.

Experiments were conducted to determine the protein efficiency ratio (PER) and net protein ratio (NPR) of meat and bone meals containing 24 or 34% ash, poultry by-product meals containing 7 or 16% ash, lamb meals containing 15 or 24% ash, a lamb meal analog containing 19% ash (mixture of lamb meal and turkey meal), and two meat and bone meals processed at either a low or a high temperature. The PER values (weight gain per unit of protein intake) and NPR values (PER corrected for maintenance) were determined using a chick growth assay in which chicks were fed a N-free diet or 10% CP diets containing one of the animal meals as the only source of dietary protein for 6, 9, or 13 d. The PER of the lamb meal analog was greater (P < 0.05) than that of the other meals, and the PER values of the poultry by-product meals were generally greater than those for the lamb and meat and bone meals. The PER values for the lamb meals were higher than those for most of the meat and bone meals. The PER of the 34% ash meat and bone meal was lower (P < 0.05) than the PER of the 24% ash meat and bone meal (1.03 vs 1.63, respectively, at 9 d). Further experiments showed that the lower PER of the high ash meat and bone meal was not due to its high Ca and P content. Ash content had no significant effect on PER of the poultry by-product and lamb meals. The PER of the low-temperature meat and bone meal was higher (P < 0.05) than the PER of the high-temperature meat and bone meal. The relative differences in NPR values among the animal meals were similar to those observed for PER values. Decreasing the length of the assay from 13 to 6 d increased the PER and NPR of all meals but had little or no effect on the ranking of values among meals. The results of this study indicated that PER and NPR values of animal meals were influenced by raw material source, and that ash content and processing temperature affected the PER and NPR of meat and bone meal. The results also indicated that PER and NPR assays could be reduced to 6 d without reducing sensitivity.

Analysis of Variance↗
PubMed1997

Uterine growth, cell proliferation, and c-fos proto-oncogene expression throughout the estrous cycle in ewes.

Uterine growth, cell proliferation, and endometrial expression of the c-fos proto-oncogene were evaluated for nonpregnant ewes (n = 6 ewes per day) on Days 0 (estrus), 2, 4, 8, 12, and 15 of the estrous cycle. Fresh and dry weights of uterine horns decreased (p < 0.01) linearly from Days 0 to 8 and then remained similar from Day 8 through Day 15. Tissue water content (1 - [dry weight/fresh weight]) was greater on Day 0 (p < 0.01) than on Days 2, 4, and 8, and the latter values were greater (p < 0.01) than on Days 12 and 15. DNA content was similar on Days 0, 2, 4, 8, and 15 but increased (p < 0.01) on Day 12. Although DNA content was greatest on Day 12, the ratios of RNA to DNA and of protein to DNA were least (p < 0.01) on that day. Thus, changes in uterine fresh weight were associated primarily with changes in tissue hypertrophy (RNA:DNA and protein:DNA ratios) and water content. In addition, changes in uterine fresh weight were associated with changes in the ratio of estradiol to progesterone in systemic blood, which was greatest (p < 0.01) on Days 0 and 2, decreased (p < 0.01) from Day 2 to Day 8, remained low through Day 12, and then was elevated again (p < 0.01) on Day 15. Moreover, compartmentalized changes in endometrial cell proliferation (labeling index [LI]; percentage of cells exhibiting nuclear incorporation of bromodeoxyuridine, a thymidine analogue) also were associated with the changes in fresh weight. The epithelium of the uterine lumen and luminal glands exhibited the greatest changes in rate of cell proliferation and accounted for most of the changes in LI seen across days of the estrous cycle. Endometrial expression of c-fos mRNA and protein also reflected changes in uterine weight and the systemic estradiol:progesterone ratio. The level of c-fos mRNA was greatest at estrus, low on Days 2-8, and elevated slightly on Days 12 and 15; Fos protein was greatest on Days 0 through 4, least on Day 8, and intermediate on Days 12 and 15. Characterization of uterine growth, cell proliferation, and c-fos expression throughout the estrous cycle will provide a foundation for future studies of gene expression regulating growth of the nonpregnant uterus.

Animals↗
PubMed1997

Effects of ovarian steroids on uterine growth, morphology, and cell proliferation in ovariectomized, steroid-treated ewes.

Uterine growth, morphology, and endometrial cell proliferation were evaluated in intact estrous (EST; Day 0 of the estrous cycle) or luteal (LUT; Day 10 of the estrous cycle) ewes or in ovariectomized ewes receiving no hormone (OVX); estradiol-17beta (OVX+E); progesterone for 8 (OVX+P8), 30 (OVX+P30), or 60 (OVX+P60) days; estradiol followed by progesterone (OVX+E+P); or progesterone followed by estradiol (OVX +P+E). Uterine weights were greater for EST than for LUT ewes, were reduced 2- to 4-fold in OVX ewes, and were increased in estradiol-treated (OVX+E, OVX+E+P, and OVX+P+E) ewes. The effects of estradiol treatment on uterine growth in OVX ewes were primarily on cellular hypertrophy rather than hyperplasia. Endometrial labeling index (LI) was greater for EST than for LUT ewes and was low in OVX ewes. Compared with OVX ewes, OVX+E and OVX+P+E ewes had increased LI for all endometrial tissues, whereas OVX+P8 and OVX+E+P ewes had increased LI only for luminal epithelium. These data will help us determine the mechanisms by which ovarian steroids regulate uterine growth in ewes.

Animals↗
PubMed1997

International Classification of Diseases, 9th Revision, Clinical Modification codes in discharge abstracts are poor measures of complication occurrence in medical inpatients.

OBJECTIVES: The authors tested the ability of International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes in discharge abstracts to identify medical inpatients who experienced an in-hospital complication, using complications identified through chart review as the gold standard. METHODS: Two sets of ICD-9-CM codes were used: an inclusive set including many medical diagnoses that may also be coexistent complicating conditions on admission rather than complications and an exclusive set consisting primarily of ICD-9-CM-specified complication and adverse drug event codes. RESULTS: Neither set performed well as a diagnostic test for complication occurrence according to receiver operating characteristic analysis (ROC areas were 0.61 for the inclusive set and 0.55 for the exclusive set). Sensitivities of the ICD-9-CM codes for complications were 0.34 for the inclusive set and 0.14 for the exclusive set. Corresponding positive predictive values were 0.32 and 0.37, respectively. Sensitivities of code definitions for individual complications were generally poor, less than 0.5 in most cases. CONCLUSIONS: The authors conclude that ICD-9-CM codes in discharge abstracts are poor measures of complication occurrence.

Abstracting and Indexing↗
PubMed1997

Aging alters feed-forward and feedback linkages between LH and testosterone in healthy men.

To discern the effect of aging on coordinate luteinizing hormone (LH) and testosterone secretion, we sampled healthy older men (age 62-74 yr, n = 11) and young controls (age 21-34 yr, n = 13) every 2.5 min overnight. Deconvolution analysis and cross-correlation were used to relate serum LH concentrations to calculated testosterone secretion rates (feed-forward stimulation), as well as serum testosterone concentrations to computed LH secretion rates (feedback inhibition). Despite statistically similar mean serum LH and testosterone concentrations in the young and older men, older individuals had diminished feed-forward stimulation of LH concentrations on calculated testosterone secretion rates, as well as delayed feedback inhibition of testosterone concentrations on computed LH secretion rates.

Adult↗
PubMed1997

Caregiving: concept analysis and outcomes.

More than ever before, caregiving has become a salient public policy issue. A number of recent and anticipated demographic, economic and social changes have occurred that make it imperative for researchers to critically examine the impact of caregiving on family caregivers' health, behavior, emotions, and social status. Researchers at the University of Iowa College of Nursing are working to classify standardized nursing-sensitive patient outcomes for use in language development, practice, research, and education to evaluate the effectiveness of nursing interventions and clinical nursing services. This article focuses on family caregiving and the analysis of caregiver role performance in both direct and indirect care, linking outcomes and indicators, to enable nurses to promote the health of caregivers.

Caregivers↗
PubMed1996

HLA-DQB1 codon 57 is critical for peptide binding and recognition.

The association of specific HLA-DQ alleles with autoimmunity is correlated with discrete polymorphisms in the HLA-DQ sequence that are localized within sites suitable for peptide recognition. The polymorphism at residue 57 of the DQB1 polypeptide is of particular interest since it may play a major structural role in the formation of a salt bridge structure at one end of the peptide-binding cleft of the DQ molecules. This polymorphism at residue 57 is a recurrent feature of HLA-DQ evolution, occurring in multiple distinct allelic families, which implies a functional selection for maintaining variation at this position in the class II molecule. We directly tested the amino acid polymorphism at this site as a determinant for peptide binding and for antigen-specific T cell stimulation. We found that a single Ala-->Asp amino acid 57 substitution in an HLA-DQ3.2 molecule regulated binding of an HSV-2 VP-16-derived peptide. A complementary single-residue substitution in the peptide abolished its binding to DQ3.2 and converted it to a peptide that can bind to DQ3.1 and DQ3.3 Asp-57-positive MHC molecules. These binding studies were paralleled by specific T cell recognition of the class II-peptide complex, in which the substituted peptide abolished T cell reactivity, which was directed to the DQ3.2-peptide complex, whereas the same T cell clone recognized the substituted peptide presented by DQ3.3, a class II restriction element differing from DQ3.2 only at residue 57. This structural and functional complementarity for residue 57 and a specific peptide residue identifies this interaction as a key controlling determinant of restricted recognition in HLA-DQ-specific immune response.

Alanine↗
PubMed1996

Distance distributions from the tyrosyl to disulfide residues in the oxytocin and [Arg8]-vasopressin measured using frequency-domain fluorescence resonance energy transfer.

We have examined the fluorescence intensity decays of oxytocin and [Arg8]-vasopressin resulting from the single tyrosyl residue in each peptide, and the intensity decay of the Asu1,6-analogues in which the disulfide bridge is substituted by a CH2-CH2 bridge. Viscosity-dependent steady state and intensity decay measurements indicated that fluorescence resonance energy transfer (FRET) from tyrosyl phenol to the disulfide bridge is responsible for the decrease in fluorescence relative to the Asu-analogues. The frequency-domain phase and modulation data for the tyrosyl donor were interpreted in terms of fluorescence resonance energy transfer (FRET) to the weakly absorbing disulfide bridge and a distribution of donor-to-acceptor distances. Energy transfer efficiencies were determined from both time-resolved and steady-state measurements. Fitting the frequency-domain phase and modulation data to a Gaussian distance distribution indicated that the average inter-chromophoric distance (Rav) is similar in both compounds, Rav = 7.94 A for oxytocin and Rav = 8.00 A for vasopressin. However, the width of the distance distribution is narrower for vasopression (hw = 2.80 A) than for oxytocin (hw = 3.58 A), which is consistent with restriction of the tyrosine phenol motion due to its stacking wih the Phe3 side chain of vasopressin. Finally, the recovered distance distribution functions are compared with histograms describing the distance between the chromophores during the course of long, in vacuo, molecular dynamics runs using the computer program CHARMm and the QUANTA 3.0 parameters.

Amino Acid Sequence↗
PubMed1996

Gap junctional protein connexin 43 in bovine corpora lutea throughout the estrous cycle.

The present study examined the pattern of expression of the gap junctional protein connexin 43 (Cx43) in bovine corpora lutea (CL) during growth, differentiation, and regression. CL from the early (n = 6), mid- (n = 6), and late (n = 6) luteal phases of the estrous cycle were weighed and divided into several portions. One portion of each CL was frozen in liquid nitrogen for evaluation of protein, DNA, progesterone, and presence of Cx43 by Western immunoblot analysis; another portion was frozen in liquid propane for immunofluorescent staining of Cx43. An additional portion of each CL was dispersed, and the luteal cells were cultured for 2 days, fixed, and used for immunofluorescent staining of Cx43. Weights and DNA, protein, and progesterone contents of CL increased (p < 0.05) from the early to mid-luteal phases and then decreased (p < 0.05) from the mid- to late luteal phases. The ratio of protein to DNA was similar in the early and mid-luteal phases and then decreased (p < 0.05) to the late luteal phase. Western immunoblot analysis revealed bands at 43 kDa that differed in volume (evaluated by densitometry); the early luteal phase volume was greater (p < 0.05) than that at the mid-luteal phase, which was greater (p < 0.05) than that at the late luteal phase. Immunofluorescent staining demonstrated that Cx43 was present in luteal tissues and cultured luteal cells throughout the estrous cycle, and the area of positive staining decreased (p < 0.05) as the estrous cycle progressed. Staining for Cx43 was punctate and localized to the cellular borders. Thus, levels of Cx43 in bovine CL are greatest early in the estrous cycle and are least late in the estrous cycle. These data demonstrate that gap junctions may be important for regulation of luteal growth, differentiation, and regression in the cow.

Animals↗
PubMed1996

Estrogen and progesterone receptors, cell proliferation, and c-fos expression in the ovine uterus during early pregnancy.

To evaluate uterine growth during pregnancy and the potential roles of estrogen and progesterone in regulating uterine cell proliferation and c-fos expression, ewes were assigned randomly to slaughter on day 12 after estrus (nonpregnant, NP), and on days 12, 18, 24, or 30 after mating (pregnant, P) in Exp 1 (n = 7 ewes/day) and on days 12 or 14 after estrus and on days 12, 14, 16, 18, 21, or 24 after mating in Exp 2 (n = 3-6 ewes/day). In Exp 1, endometrial expression of c-fos mRNA was evaluated, and labeling index was determined both in vitro (incorporation of 3H-thymidine) and in vivo (iv injection of bromodeoyxuridine [BrdU], a thymidine analog). Endometrial expression of the c-fos proto-oncogene was increased by approximately 10-fold on days 18, 24, and 30 P compared with day 12 NP or P. Labeling index (proportion of cells incorporating 3H-thymidine or BrdU, which provides an index of the rate of cell proliferation) of endometrial caruncular and intercaruncular tissues was low for day 12 NP or P, increased on day 18 P, and remained elevated on days 24 P and 30 P. On day 18 P, labeling index also was greater for gravid than nongravid horns for both caruncular and intercaruncular tissues. In Exp 2, estrogen receptors (ER), progesterone receptors (PR), and proliferating (BrdU-positive) cells were immunolocalized. The percentage of cells exhibiting specific staining for ER, PR, and BrdU was quantified morphometrically for epithelial, stromal, and glandular tissues within luminal and deep regions, as well as for myometrial tissues. For luminal epithelium and glands, the rate of cell proliferation increased dramatically by day 18 P, even though ER and PR levels were low in these compartments. Conversely, the rate of cell proliferation remained low throughout early pregnancy in deep glands, deep stroma, and myometrium, in association with sustained or transient increases in ER and PR levels. For luminal stroma, the rate of cell proliferation increased by day 21 P even though ER levels were low and PR levels remained high. Thus, during early pregnancy, c-fos expression increased concomitantly with increased endometrial cell proliferation. In addition, during early pregnancy, ER and PR levels were inversely related to the rate of cell proliferation in most of the uterine tissue compartments except luminal stroma, which exhibited increased cell proliferation even though ER levels were low and PR levels remained high.

Animals↗
PubMed1996

Is growth saltatory? The usefulness and limitations of frequency distributions in analyzing pulsatile data.

Several investigators have proposed that descriptive statistics can be employed to identify and discriminate growth patterns. These studies assumed that the shape of the frequency distribution of daily growth velocities (FDGVs) is diagnostic in differentiating between a pattern of growth characterized by smooth, continuous daily acquisition and a pattern of growth characterized by a discontinuous, i.e. pulsatile process. The FDGV from a saltation and stasis, i.e. episodic or pulsatile, growth pattern was assumed to be bimodal or significantly skewed to the right, whereas a continuous growth function was assumed to be approximately Gaussian. The use of FDGV characteristics is an unprecedented approach to the analysis of longitudinal growth data and was not previously validated for this use. The present study investigates the performance characteristics of the FDGV method by Monte-Carlo simulations of known saltatory, i.e. pulsatile, growth patterns. These analyses show that the FDGV for a saltation and stasis growth process can be either unimodal or bimodal and either skewed to the right or to the left. Data collection frequency, measurement error, and total study duration all determine the shape of the FDGV and the statistical significance of the results. If the FDGV is highly skewed, then it is consistent with saltatory growth. However, if the FDGV is not highly skewed, then it is consistent with both the saltatory model and a smooth, continuous growth model, and thus, the results are ambiguous. We conclude that FDGV analysis is not a valid method to exclude saltation and stasis growth processes in longitudinal growth studies.

Child Development↗
PubMed1996

Multifactorial control of the elimination kinetics of unbound (free) growth hormone (GH) in the human: regulation by age, adiposity, renal function, and steady state concentrations of GH in plasma.

To evaluate the principal determinants of the MCR and plasma t1/2 of unbound (free) GH in man, we performed steady state infusions of 3 doses of recombinant human GH during pharmacological suppression (iv octreotide) of endogenous GH secretion in 24 healthy adults and 12 patients (6 adults and 6 children) with chronic renal failure (CRF). Free plasma GH was calculated from total plasma GH (measured by immunoradiometric assay) and GH-binding protein activity (radioligand assay). The MCR of free GH was determined from free plasma GH and the rate of recombinant human GH infusion. The t1/2 of free plasma GH, and the concentration and the in vivo dissociation constant (Kd) of GH-binding protein (GHBP) were estimated by dynamic modeling of the postinfusion total plasma GH concentration decay curves. The MCR of free GH decreased and the plasma GH t1/2 increased significantly with increasing plasma GH concentrations. The MCR of free GH over its physiological concentration range was positively correlated with the body mass index as a measure of relative obesity and negatively related to age, but only at supraphysiological GH concentrations. In the adult patients with CRF, the MCR of free GH was decreased at each infusion rate by 25-38%, and the t1/2 was increased by 80-170%. Children with CRF showed a significantly lower MCR and higher t1/2 of plasma free GH than adult patients. Modeling and direct measurements of the off-rate of GH from its high affinity GHBP indicated normal dissociation rate constants but decreased molar concentrations of the GHBP in uremic plasma. We conclude that the rate of elimination of free GH from plasma in man is controlled by 1) plasma total free GH concentrations, 2) relative obesity, and 3) renal function within the physiological GH concentration range, whereas 4) age is a negative predictor of MCR only at supraphysiological GH concentrations.

Adolescent↗