Differentially conserved transcriptomic response to adversity related to self-rated health in the multi-ethnic study of atherosclerosis.

Self-rated health (SRH) is considered a strong indicator of well-being and clinical health status and has been linked to inflammatory markers. The objective of this work was to examine how self-rated physical health (SRPH) and mental health (SRMH) influence the immune system through the regulation of a stress-related gene expression profile known as the 'conserved transcriptional response to adversity' (CTRA), which involves the up-regulation of pro-inflammatory genes and down-regulation of genes involved in type I interferon (IFN) response and antibody synthesis. CTRA expression data were derived from genome-wide transcriptional data on purified monocytes in 1264 adult participants from the multi-ethnic study of atherosclerosis. SRPH and SRMH were assessed through the SF-12 questionnaire. Multiple linear regression models were used to determine the association between the composite score of the CTRA subsets and SRPH and SRMH. Higher scores of SRPH and SRMH were associated with an increased expression of the overall CTRA profile. The individual gene subsets analysis did not reveal an increased expression of pro-inflammatory genes in persons with lower scores of SRH. However, we observed that higher scores of SRPH positively modulate the immune response through the up-regulation of both type I interferon response and antibody synthesis-related genes, while better scores of SRMH were associated with a down-regulation of genes involved in antibody synthesis. The significant association between SRH and a gene expression profile related to type I IFN response and antibody synthesis suggests that SRH may be linked to the immunocompetence status. Impact statement In this work, we evaluated for the first time how self-rated mental (SRMH) and physical health (SRPH) influence the immune response at the molecular level in a large multi-ethnic cohort. We observed that both SRMH and SRPH are related to immunocompetence status. These findings indicated that the link between how we perceive our health and poorer health outcomes could be explained by alterations in the immune response by shifting the expression of genes related to the type I IFN response and antibody synthesis.

Adiposity, lipogenesis, and fatty acid composition of subcutaneous and intramuscular adipose tissues of Brahman and Angus crossbred cattle.

The objective of this study was to demonstrate differences in aspects of adipose tissue cellularity, lipid metabolism, and fatty and cholesterol composition in Angus and Brahman crossbred cattle. We hypothesized that in vitro measures of lipogenesis would be greater in three-fourths Angus progeny than in three-fourths Brahman progeny, especially in intramuscular (i.m.) adipose tissue. Progeny ( = 227) were fed a standard, corn-based diet for approximately 150 d before slaughter. Breed was considered to be the effect of interest and was forced into the model. There were 9 breed groups including all 4 kinds of three-fourths Angus calves: Angus bulls Angus-sired F cows ( = 32), Angus bulls Brahman-sired F cows ( = 20), Brahman-sired F bulls Angus cows ( = 24), and Angus-sired F bulls Angus cows ( = 20). There were all 4 kinds of three-fourths Brahman calves: Brahman bulls Brahman-sired F cows ( = 21), Brahman bulls Angus-sired F cows ( = 43), Brahman-sired F bulls Brahman cows ( = 26), and Angus-sired F bulls Brahman cows ( = 13). Additionally, F calves (one-half Brahman and one-half Angus) were produced only from Brahman-sired F bulls Angus-sired F cows ( = 28). Contrasts were calculated when breed was an important fixed effect, using the random effect family(breed) as the error term. Most contrasts were nonsignificant ( > 0.10). Those that were significant ( < 0.05) included cholesterol concentration of subcutaneous (s.c.) adipose tissue (three-fourths Angus > F, three-fourths Brahman > F, and three-fourths crossbred progeny combined > F), s.c. adipocyte volume (three-fourths Angus > F and three-fourths bloods combined > F), lipogenesis from acetate in s.c. adipose tissue (three-fourths Brahman calves from Brahman dams > three-fourths Brahman calves from F dams), and percentage 18:3-3 in s.c. adipose tissue (three-fourths Brahman calves from Brahman-sired F dams < three-fourths Brahman calves from Angus-sired F dams). Intramuscular adipocyte volume ( < 0.001) was less in three-fourths Brahman cattle than in three-fourths Angus cattle. Additionally, several differences were observed in i.m. adipose tissue that were consistent with this being a less-developed adipose tissue in three-fourths Brahman cattle than in three-fourths Angus cattle.

Estimation of genotype distributions and posterior genotype probabilities for beta-mannosidosis in Salers cattle.

beta-Mannosidosis is a lethal lysosomal storage disease inherited as an autosomal recessive in man, cattle and goats. Laboratory assay data of plasma beta-mannosidase activity represent a mixture of homozygous normal and carrier genotype distributions in a proportion determined by genotype frequency. A maximum likelihood approach employing data transformations for each genotype distribution and assuming a diallelic model of inheritance is described. Estimates of the transformation and genotype distribution parameters, gene frequency, genotype fitness and carrier probability were obtained simultaneously from a sample of 2,812 observations on U.S. purebred Salers cattle with enzyme activity, age, gender, month of pregnancy, month of testing, and parents identified. Transformations to normality were not required, estimated gene and carrier genotype frequencies of 0.074 and 0.148 were high, and the estimated relative fitness of heterozygotes was 1.36. The apparent overdominance in fitness may be due to a nonrandom sampling of progeny genotypes within families. The mean of plasma enzyme activity was higher for males than females, higher in winter months, lower in summer months and decreased with increased age. Estimates of carrier probabilities indicate that the test is most effective when animals are sampled as calves, although effectiveness of the plasma assay was less for males than females. Test effectiveness was enhanced through averaging repeated assays of enzyme activity on each animal. Our approach contributes to medical diagnostics in several ways. Rather than assume underlying normality for the distributions comprising the mixture, we estimate transformations to normality for each genotype distribution simultaneously with all other model parameters. This process also excludes potential biases due to data preadjustment for systematic effects. We also provide a method for partitioning phenotypic variation within each genotypic distribution which allows an assessment of the value of repeat measurements of the predictive variable for genotype assignment.

Modulation of growth hormone (GH) secretion and GH mRNA levels by GH-releasing factor, somatostatin and secretagogues in cultured bovine adenohypophysial cells.

The effects of endogenous hypothalamic neurohormones and activators of second messenger signalling systems on the secretion of GH and on cell content of GH mRNA of cultured bovine adenohypophysial cells were studied. Synthetic bovine GH-releasing factor (bGRF; 100 nmol/l) increased secretion of GH by bovine adenohypophysial cells five-fold relative to control. Forskolin (an adenyl cyclase activator; 10 mumol/l) and the synthetic cyclic AMP analogue dibutyryl cyclic AMP (dbcAMP; 1 mmol/l) increased secretion of GH by 1.9- and 1.7-fold respectively, relative to control. The protein kinase C activator phorbol 12-myristate 13-acetate (PMA), provided at 1 mumol/l or 10 nmol/l, increased GH secretion by 6.6- and four-fold respectively, relative to control. Somatostatin-14 (SRIF-14) attenuated basal, bGRF-, forskolin- and dbcAMP-stimulated secretion of GH by 40, 49, 47 and 67% respectively, but did not, however, diminish PMA-stimulated GH secretion. The content of GH mRNA in cultured bovine adenohypophysial cells increased 2.2-, 1.7- and 3.2-fold by administration of bGRF, forskolin and PMA respectively, relative to control. Although GH mRNA content was unchanged by SRIF-14 treatment relative to control, SRIF-14 did reduce bGRF-stimulated bGH mRNA content by 67%. This study demonstrates that mechanisms subserving GH secretion in bovine adenohypophysial cells (e.g. adenyl cyclase and protein kinase C) may be coupled with mechanisms which regulate expression of the GH gene or with factors affecting message stability.

Increasing disparity in knowledge of cardiovascular disease risk factors and risk-reduction strategies by socioeconomic status: implications for policymakers.

During the 1980s extensive local and national cardiovascular health promotion campaigns were implemented to improve knowledge of risk reduction. This study analyzed changes from 1980 to 1990 in knowledge of acquired cardiovascular risk factors (i.e., actual, objective knowledge of adverse lifestyle factors affecting cardiovascular health); perceived knowledge of risk-reduction strategies (i.e., subjective knowledge about how to reduce the likelihood of cardiovascular disease); and interest in risk modification (i.e., interest in changing risk-factor habits) by socioeconomic status using level of education. The study population included 2,455 women and men 25-74 years of age from three population-based cross-sectional surveys in two northern California cities. We found significant differentials in baseline knowledge that widened over the 10-year study period, resulting in larger disparities across educational groups at the final survey in 1990 (P < .05). From 1980 to 1990, individuals with < 12 years of education experienced only slight improvement in their knowledge of cardiovascular risk factors (mean summary score of 4.4 increasing to 5.5, based on a 17-item questionnaire of risk factors); those with > or = 16 years of education experienced twice as much improvement (mean of 8.4 increasing to 11.1) (P < .05). There were similar time-effect disparities in knowledge of risk-reduction strategies (P < .05). In contrast, interest in risk modification was high for all educational groups and remained uniform across time. The continuing and widening disparity in knowledge between socioeconomic groups suggests the need for policymakers to reform existing cardiovascular risk-reduction education campaigns.

Determinants of cholesterol screening and treatment patterns. Insights for decision-makers.

BACKGROUND: Adult cholesterol screening and treatment policies by the National Cholesterol Education Program recommend that physicians screen all adults aged > 20 [corrected]. On the other hand, the American College of Physicians recommends that healthy young adult men aged > 35 and premenopausal women aged > 45 not be screened due to concerns about the cost of and health risks associated with overuse of pharmacologic therapy in lieu of lifestyle modification. OBJECTIVES: The objectives of this study were to determine the type of treatment (lifestyle vs. pharmacologic) that physicians actually prescribe for individuals screened for elevated cholesterol. METHODS: Self-report data were derived from the 1989-1990 cross-sectional survey of the Stanford Five-City Project on 1,883 Latino and Anglo men and women aged 20 to 74 years of age. A four-stage sequential design was conducted using multiple stepwise regression analyses with a significance cutpoint of P < .01. RESULTS: Young adult men and women were significantly less likely to report ever having been screened (OR 1.02; 95% CI 1.07-1.09). Individuals of low socioeconomic status (SES) were also significantly less likely to report ever being screened (OR, 1.12; CI, 1.08-1.16), as were Latino men and women, regardless of age (OR 1.57; CI, 1.14-2.18). There were no significant differences in the pattern of physician care utilization among low SES or Latino individuals during the previous 12-month period. Among those under physician care to lower cholesterol, young adults were more likely to be prescribed lifestyle modification (OR, 0.95; CI, 0.92-0.98). CONCLUSIONS: Our results suggest that although young adults are less likely to be screened, if screened they are more likely to be prescribed lifestyle modification than pharmacologic treatment for elevated cholesterol. The lower prevalence of screening among low SES and Latino individuals suggests the need for policy discussions to reduce these disparities.

Genomic sequencing of the bovine T cell receptor beta locus.

The T cell, which plays an integral role in the coordination of the immune system, has a heterodimer receptor (TCR) that can exist in one of the two forms: alpha/beta or gamma/delta. Cells displaying the gamma/delta TCR comprise less than 5% of T cell populations in humans and mice. In the bovine system, however, gamma/delta populations can reach as high as 60%. Differences in T cell populations make the bovine system an excellent candidate for genomic TCR sequencing and multi-species comparisons. In an effort to characterize the bovine TCR loci, a genomic library was screened for the beta TCR gene. A shotgun sequencing library was constructed and preliminary analysis demonstrates that the organization of the bovine TCR beta constant regions is different from both humans and mice. The bovine beta locus appears to have a third constant region. Overall, the genomic characterization of the bovine TCR genes will provide insight into the evolution of T cell receptor.

Chemical dependency in women: a description of its effects and outcome on adequate parenting.

The purpose of this article is to define chemical dependency in women as a maladaptive response to inadequate upbringing. A description of the situational and psychological variables that characterize chemically dependent women is offered as well as attributes these women lack that are necessary for effective parenting. The dysfunctional child-rearing patterns and the consequential outcome for the children are also described. Suggestions for clinical intervention are provided.

Nematode burdens and cellular responses in the abomasal mucosa and blood of Florida Native, Rambouillet and crossbreed lambs.

This experiment was carried out to compare the worm burden and cellular responses in the abomasal mucosa and blood of Florida Native and Rambouillet lambs and also in animals produced by crosses of these two breeds (generations F1 and F2). Animals were exposed to infection by gastrointestinal nematodes on three different occasions. The first infection was natural, occurring while they were suckling lambs. After weaning, they were kept indoors for 53 days and then were allowed to graze a contaminated pasture for 50 days for a second natural infection. The third infection was an artificial challenge with 6000 Haemonchus contortus infective larvae. The highest mean fecal egg counts (FEC) values were found in Rambouillet lambs followed in decreasing order by F1, F2 and Florida Native lambs. Throughout the trial, most of the high mean packed cell volumes and plasma protein levels were recorded in the F2 lambs; in contrast, most of the low values were found in the Rambouillet lambs. During the natural infection period, the highest percentages of larvae in the fecal cultures of the lambs were Haemonchus. However, high percentages of Trichostrongylus larvae were found particularly in Florida Native lambs. The mean number of blood eosinophils increased after the artificial challenge, reached a peak 21 days after infection and then declined. The highest and lowest blood eosinophil means were recorded in F2 and Florida Native lambs, respectively. The H. contortus burden was significantly higher in Rambouillet and in F1 lambs than in Florida Native and F2 lambs (p < 0.05), while no significant differences were recorded among eosinophil, mast cell and globule leucocyte counts in the abomasal mucosa (p > 0.05). The highest correlation coefficient recorded at the end of this study was between FEC and worm burden (r = 0.7). These two parameters showed a moderate negative correlation with PCV, plasma protein and mast cell counts in the abomasal mucosa. The results obtained in this study indicate that crossbreeding Florida Native and Rambouillet sheep can be a rapid way to combine and improve the characteristics of these two breeds. The parasitological results were promising, however, more studies will be necessary to verify the impact of crossbreeding in other traits.

Adipose tissue cellularity and muscle growth in young steers fed the beta-adrenergic agonist clenbuterol for 50 days and after 78 days of withdrawal.

Angus steers (n = 40; approximate weight = 300 kg) were administered the beta-adrenergic agonist clenbuterol for 50 d (7 mg.hd-1.d-1), followed by a 78-d withdrawal period. Carcass fatness variables did not differ (P greater than .05) between treated and control animals either after 50 d or after 128 d. Weights of the 9-10-11th rib longissimus muscle were 25% larger, and longissimus cross-sectional areas were 28% greater, in clenbuterol-fed steers relative to controls from 0 to 50 d (P less than .05). After withdrawal these measurements increased no further in the treated steers. Marbling scores were decreased (P less than .05) in clenbuterol-fed steers after 50 d of treatment; this effect persisted after 128 d of withdrawal from treatment. Shear force values were increased 19% (P less than .05) by feeding clenbuterol for 50 d and remained greater (P less than .05) in treated animals after 128 d. Subcutaneous adipocytes in clenbuterol-fed steers were smaller (P less than .05) than those of controls after 50 d, and this effect was still apparent after the 78-d withdrawal period. Rates of lipogenesis did not differ (P less than .05) between treated and control animals at any time. Perirenal (p.r.) adipocytes were smaller (P less than .05) in treated animals after 50 d, but this effect disappeared by the end of the experiment. There was no indication of a bimodal distribution of smaller s.c. or p.r. adipocytes in either of the treatment groups. Apparent hyperplasia of s.c. adipocytes occurred in the area of the 9-10-11th rib in both treated (P less than .10) and control animals (P less than .05) from 0 to 50 d on trial. Within treated animals there was a significant increase (P less than .05) in total adipocytes in this depot during the withdrawal period. Although the effects of clenbuterol on muscle growth generally were reversed after 78 d, the effects of the beta-adrenergic agonist on adipose tissue development were more permanent.

Elevation of a specific mRNA in longissimus muscle of steers fed ractopamine.

To address the hypothesis that some classes of growth promoters stimulate muscle protein synthesis in growing cattle, 23 crossbred steers were fed diets containing the phenethanolamine growth promoter ractopamine in a 140-d feeding trial. Steers received either no ractopamine, .18 or .36 mg.kg BW-1.d-1 ractopamine for 140 d or .36 or .72 mg.kg BW-1.d-1 ractopamine for 56 d. Longissimus muscle was obtained at slaughter and frozen in liquid N2. RNA was extracted by homogenization of pulverized frozen muscle in guanidinium isothiocyanate and centrifugation through cesium chloride. Polyadenylated mRNA was extracted by capture on oligo-dT columns. Ractopamine had no effect on total RNA or mRNA concentrations (P greater than .25). Hybridization of the RNA to a putative myosin light chain-1/3 (MLC-1/3) cDNA clone in a Northern blot indicated one heavy band (approximately 1 kb) with no evidence of extensive destruction of the RNA. A second, minor band (approximately 3 kb) also was observed in some samples. The MLC-1/3 cDNA clone was hybridized to 1- or 5-micrograms samples of total RNA, and the intensity of the resultant autoradiographs was quantified by laser densitometry. There was a statistical correlation between MLC-1/3 mRNA-micrograms RNA-1 and longissimus cross-sectional area (P less than .05) and average daily gain (P less than .025). The results suggest that ractopamine either increased the transcription of the putative MLC-1/3 gene and(or) increased the stability of MLC-1/3 mRNA in bovine longissimus muscle, either of which could result in an increase in specific myofibrillar protein synthesis.

Tissue-specific activity of pentose cycle oxidative enzymes during feeder lamb development.

Relationships between pentose cycle oxidative activity and differential fat growth were evaluated. Rambouillet wether lambs (n = 60) were slaughtered serially at 0, 40, 80, and 120 d on feed (15 lambs/group). Rack dissection and kidney fat weights were collected, and longissimus muscle i.m. fat content was determined. Postmortem longissimus muscle, s.c. fat, intermuscular fat (INT), and kidney fat (KP) samples were assayed in vitro for glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) activity (nanomoles.minute-1.gram of tissue-1), and samples were subjected to electrophoresis (PAGE) to separate tissue-specific isoforms. Allometric coefficients for rack components indicated that s.c. fat was the earliest-maturing, slowest-growing depot, INT was the latest-maturing, fastest-growing depot, and i.m. fat was intermediate (P < .05). Kidney fat grew faster than carcass weight and, as carcass weight increased, the growth rate of KP accelerated (P < .05). Enzyme activities increased until 40 d on feed and declined thereafter. Activities differed across tissues and time on feed end points (P < .05). Ratios of G6PDH:6PGDH, reflecting flux through the oxidative phase of the pentose cycle and, therefore, lipogenic activity, suggested growth patterns similar to those indicated by allometric analysis, except in the i.m. fat depot. Development of i.m. fat initially was intermediate to KP and INT, but G6PDH:6PGDH ratios increased with time on feed, suggesting a different regulatory mechanism and maturing pattern. Multiple forms of G6PDH were detected with PAGE, and although polymorphism was not detected, a tissue-specific isoform was isolated for INT fat.

Comprehensive interventions for affecting the parenting effectiveness of chemically dependent women.

Research suggests that the ineffective parenting techniques used by many chemically dependent women may be as much a result of pre-existing conditions, such as traumatic childhood experiences, negative affective states, and ineffective social support networks, as from actual substance abuse. Comprehensive interventions are needed that address these pre-existing conditions along with drug and alcohol issues to maximize the parenting outcomes of chemically dependent women. The sequence of appropriate interventions in the areas of assessments, treatment, parenting education, and pregnancy and health needs as they relate to the quality of parenting among chemically dependent women are discussed. The role of the health care provider is discussed, and suggestions about referrals and resources are identified.

Perceptions by the aged of crime, criminals, and the criminal justice system.

A general fear of crime victimization led to modified activities in the community and feelings of relative safety in their own area for 132 elderly respondents on a 24-item questionnaire. They held sympathetic views of crime perpetrators as disadvantaged victims of society themselves, but came to the unlikely conclusions that more police control and harsher prison sentences are needed.

Use of staff pharmacists to reduce the inappropriate use of parenteral histamine-2 antagonist therapy.

This article describes the development and implementation of a target drug monitoring program using staff pharmacists as primary data collectors. This target drug program increased professional activities of staff pharmacists and showed how pharmacists could make an impact on drug therapy both financially and clinically. Parenteral histamine-2 antagonists were selected based upon amount of use and potential for inappropriate use and dosing. Criteria were developed in conjunction with the Pharmacy and Therapeutics Committee and medical staff. In phase I, pharmacists prospectively monitored all patients receiving parenteral cimetidine and ranitidine. Therapy was reviewed for justification of parenteral therapy (vs. oral), dosage adjustment in renal impairment, and monitoring of specific drug-drug interactions with cimetidine or ranitidine. During this phase, pharmacists collected data without intervening. Results from phase I and a program proposal for phase II were approved by the Pharmacy and Therapeutics Committee. Phase II consisted of the same monitoring procedures; however, when inconsistencies with the criteria were identified in one of the three categories, "chart education sheets" were placed in the chart. Results from phase I indicated a potential for cost savings. During phase II, 45% of the inappropriate parenteral therapy was changed to oral therapy, representing an annualized cost savings of $23,321 in this 540-bed hospital. The pharmacists were also successful in adjusting doses in renal impairment and monitoring potential drug interactions. The target drug program has proved to be an effective method of educating physicians and decreasing costs to the institution without the use of additional personnel.

Diversity and Generation X.

Managing Generation X (1965-1980) to be of better service to patients and organizations is a challenge for nurse managers. This article provides action scenarios that assist in understanding diversity and generations.

Evolution of the 28S ribosomal RNA gene in anurans: regions of variability and their phylogenetic implications.

Fifteen restriction sites were mapped to the 28S ribosomal RNA gene of individuals representing 54 species of frogs, two species of salamanders, a caecilian, and a lungfish. Eight of these sites were present in all species examined, and two were found in all but one species. Alignment of these conserved restriction sites revealed, among anuran 28S rRNA genes, five regions of major length variation that correspond to four of 12 previously identified divergent domains of this gene. One of the divergent domains (DD8) consists of two regions of length variation separated by a short segment that is conserved at least throughout tetrapods. Most of the insertions, deletions, and restriction-site variations identified in the 28S gene will require sequence-level analysis for a detailed reconstruction of their history. However, an insertion in DD9 that is coextensive with frogs in the suborder Neobatrachia, a BstEII site that is limited to representatives of two leptodactylid subfamilies, and a deletion in DD10 that is found only in three ranoid genera are probably synapomorphies.