Biomedical subjects

J Baron

Publications and source records attributed to J Baron.

At least 19 recordsLinked to original sources

PubMed2006

[In vitro allergy testing].

Along with the history, skin tests and provocation tests, in vitro test procedures are essential for the adequate care for patients with allergies. While serological investigations of immediate-type allergic reactions primarily detect allergen-specific IgE antibodies, basophil activation tests with different read-out parameters are available for cellular diagnosis of immediate-type reaction patterns. If clinically necessary, further immunological methods (i. e. immunoblots, lymphocyte transformation tests) can be employed. New options are provided by allergen microarray technology, which makes it possible to determine not only the specific antigenic protein but also to analyze different epitopes.

Allergens↗

PubMed2004

Early regional assessment of LV mass regression and function after stentless valve replacement: comparative randomized study.

Early regional performance and hypertrophy regression after stentless aortic valve replacement are still incompletely characterized. We compared early postoperative changes of segmental thickness and function after stentless and stented aortic valve replacement as assessed by cardiac magnetic resonance (CMR). In 16 patients randomly assigned to stented (Mosaic, 8 patients) and stentless (Freestyle, 8 patients) groups, 4 parallel short-axis images at the level of the apex (slice 4), midventricle (slices 2-3), and mitral valve (slice 1) were obtained with a 1.5 T CMR scanner (Magnetom Sonata, Siemens) before and 1 month after surgery. Cine images were obtained using an echo gradient sequence. Left ventricle mass was calculated as the difference between the left ventricular end-diastolic volume at the epicardial and endocardial borders multiplied by a myocardium density factor (1.05). Each slice was divided into 8 segments (octants) from anterior (octant I-II) to septal (octant V-VIII). A total of 32 segments encompassed the entire heart. From each of these elements end diastolic thickness and systolic function (fractional thickening) were calculated. In stentless valves significant reduction of septal octant thickness on the midventricular slice was noted. There was no difference in regional systolic function-segment thickening. In stented valves no segmental thickness changes were observed. In stentless valves there was early postoperative thickness reduction of septal segments at the midventricular level. However, this finding did not coincide with changes in segmental function.

Aged↗

PubMed2002

Differential regulation of the expression of transporters associated with antigen processing, TAP1 and TAP2, by cytokines and lipopolysaccharide in primary human macrophages.

OBJECTIVE: Using microarray technique we analysed global changes in gene expression of interferon-y treated primary macrophages. Among the differential expressed genes identified we focussed on the expression of the transporters associated with antigen processing, TAP1 and TAP2, which are involved in the antigen presentation via MHC class 1. Patients suffering from TAP deficiency syndrome have clinical manifestations including recurrent bacterial infections of the respiratory tract and chronic necrotizing granulomatous skin lesions. This is one reason why the regulation of TAP gene expression in antigen presenting cells such as macrophages might provide important general insights into the generation of cellular immune response to multiple pathogens. Additionally IFN-alpha is important in adjuvant tumortherapie although the working mechanisms are unknown. Because of the possibility of the TAPs to be involved in these mechanisms we studied the expression of these transporters in human macrophages after stimulation with pro-inflammatory mediators. MATERIAL AND TREATMENT: Monocyte derived macrophages were treated for 24 h with either interferon-gamma, interferon-alpha, interleukin-1 (each 100 U/ml) or lipopolysaccharide (1 microg/ml). METHODS: IFN-gamma induced gene expression was analysed using microarray technique. TAP expression was investigated by RT-PCR, northern blot- and western blot analysis. RESULTS: TAP1 and TAP2 were constitutively expressed at a low level. IFN-gamma upregulated the expression of both transporters. LPS caused an increase similar to the effect of IFN-gamma. Treatment with IFN-a stimulated also the expression, however, less than IFN-y. In contrast, IL-1beta stimulation had no effect. CONCLUSION: Our data show that the transporters associated with antigen presentation are differentially regulated by pro-inflammatory mediators in human macrophages. The finding that IFN-alpha stimulates the expression of proteins involved in cytotoxic effector functions of macrophages contributes to the understanding of the immunoregulatory role of type 1 interferons and may help to explain the efficacy of IFN-alpha in the treatment of tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2002

Estrogen receptor-alpha and -beta are expressed throughout postnatal development in the rat and rabbit growth plate.

Estrogen regulates skeletal growth and promotes epiphyseal fusion. To explore the mechanisms underlying these effects we investigated the expression of estrogen receptor-alpha (ERalpha) and -beta (ERbeta) in rat and rabbit growth plates during postnatal development, using immunohistochemistry. Immunoreactivity for ERalpha and ERbeta was observed in resting zone and proliferative zone chondrocytes at all ages studied for both rat (7, 14, 28 and 70 days of age) and rabbit (1, 7, 28 and 120 days of age). In the rat distal humerus and the rabbit proximal tibia, expression of both receptors in the hypertrophic zone was minimal at early ages, increasing only at the last time point prior to epiphyseal fusion. Expression was rarely seen in the hypertrophic zone of the rat proximal tibia, a growth plate that does not fuse until late in life. Therefore, we conclude that ERalpha and ERbeta are both expressed in the mammalian growth plate. The temporal and anatomical pattern suggests that ER expression in the hypertrophic zone in particular may play a role in epiphyseal fusion.

Aging↗

PubMed2001

Effects of estrogen on growth plate senescence and epiphyseal fusion.

Estrogen is critical for epiphyseal fusion in both young men and women. In this study, we explored the cellular mechanisms by which estrogen causes this phenomenon. Juvenile ovariectomized female rabbits received either 70 microg/kg estradiol cypionate or vehicle i.m. once a week. Growth plates from the proximal tibia, distal tibia, and distal femur were analyzed after 2, 4, 6, or 8 weeks of treatment. In vehicle-treated animals, there was a gradual senescent decline in tibial growth rate, rate of chondrocyte proliferation, growth plate height, number of proliferative chondrocytes, number of hypertrophic chondrocytes, size of terminal hypertrophic chondrocytes, and column density. Estrogen treatment accelerated the senescent decline in all of these parameters. In senescent growth plates, epiphyseal fusion was observed to be an abrupt event in which all remaining chondrocytes were rapidly replaced by bone elements. Fusion occurred when the rate of chondrocyte proliferation approached zero. Estrogen caused this proliferative exhaustion and fusion to occur earlier. Our data suggest that (i) epiphyseal fusion is triggered when the proliferative potential of growth plate chondrocytes is exhausted; and (ii) estrogen does not induce growth plate ossification directly; instead, estrogen accelerates the programmed senescence of the growth plate, thus causing earlier proliferative exhaustion and consequently earlier fusion.

Animals↗

PubMed2001

Tethered-function analysis reveals that elF4E can recruit ribosomes independent of its binding to the cap structure.

The cap-binding complex elF4F is involved in ribosome recruitment during the initiation phase of translation and is composed of three subunits: elF4E, -4G, and -4A. The m7GpppN cap-binding subunit eIF4E binds the N-terminal region of eIF4G, which in turn contacts eIF4A through its central and C-terminal regions. We have previously shown, through a tethered-function approach in transfected HeLa cells, that the binding of eIF4G to an mRNA is sufficient to drive productive translation (De Gregorio et al., EMBO J, 1999, 18:4865-4874). Here we exploit this approach to assess which of the other subunits of elF4F can exert this function. eIF4AI or mutant forms of eIF4E were fused to the RNA-binding domain of the lambda phage antiterminator protein N to generate the chimeric proteins lambda4A, lambda4E-102 (abolished cap binding), and lambda4E-73-102 (impaired binding to both, the cap and eIF4G). The fusion proteins were directed to a bicistronic reporter mRNA by means of interaction with a specific lambda-N binding site (boxB) in the intercistronic space. We show that lambda4E-102, but neither the double mutant lambda4E-73-102 nor lambda4A, suffices to promote translation of the downstream gene in this assay. Coimmunoprecipitation analyses confirmed that all lambda-fusion proteins are capable of interacting with the appropriate endogenous eIF4F subunits. These results reveal that eIF4E, as well as eIF4G, can drive ribosome recruitment independent of a physical link to the cap structure. In spite of its interaction with endogenous eIF4G, lambda4A does not display this property. eIF4A thus appears to supply an essential auxiliary function to eIF4F that may require its ability to cycle into and out of this complex.

Amino Acid Sequence↗

PubMed2001

Allocation of transplantable organs: do people want to punish patients for causing their illness?

Some people believe patients with alcoholic cirrhosis should not receive equal priority for scarce transplantable organs. This may reflect a belief that these patients (1) are personally responsible for causing their own illnesses, (2) have poor transplant prognoses, or (3) are unworthy because they have engaged in socially undesirable behavior. We explore the roles that social desirability and personal responsibility have in people's judgments about transplant allocation. We presented prospective jurors with 4 scenarios, asking them to distribute 100 transplantable organs among 2 groups of 100 patients each. In each scenario, 1 group of patients, but not the other, was described as having a history of unhealthy behavior (alcohol or cigarette use) associated with a poorer prognosis. In some scenarios, alcohol or cigarette use was said to cause the organ failure. In others, it only contributed to the patients' transplant prognosis. We also obtained self-reports of subjects' own smoking status. Subjects allocated significantly fewer than half the organs to those with unhealthy behaviors and worse prognoses (33%; P <.001), but the specific behavior (alcohol versus cigarette use) was not significantly associated with subjects' allocation choices. Significantly fewer organs were allocated to patients with behavior responsible for causing their diseases than to other patients (P <.0001). Subjects who never smoked discriminated the most and current smokers discriminated the least against patients with a history of unhealthy behavior (P <.0001). The public's transplantation allocation preferences are influenced by whether patients' behaviors are said to have caused their organ failure.

Adult↗

PubMed2001

The role of thrombin in preterm parturition.

OBJECTIVE: Previous reports from our laboratory have shown that thrombin is a potent uterotonic agonist; those studies have suggested a role for thrombin during parturition, especially with regard to intrauterine bleeding. Thrombin activation can be quantified in peripheral blood by measurement of thrombin-antithrombin III (TAT) complex levels. This study sought to determine whether thrombin activation, as measured by thrombin-antithrombin III levels, is associated with premature labor. STUDY DESIGN: Thrombin-antithrombin III levels were measured in patients and control subjects with preterm labor. Quantitative TAT levels were determined by use of an enzyme-linked immunoassay with a working range from 0 to 60 ng/mL. All patients were monitored for pregnancy outcome. Receiver operating curve analysis was performed to determine the optimal TAT cutoff values. Further statistical analyses with one-way ANOVA, the chi2 test, or the Fisher exact test were performed to determine statistical significance (P <.05). RESULTS: Patients admitted with preterm labor who were subsequently delivered within 3 weeks had significantly higher mean TAT levels (7.80 +/- 2.86 ng/mL; P <.05) than control subjects (5.77 +/- 1.43 mL) or patients with preterm labor who were not delivered within 3 weeks of presentation with preterm labor (5.57 +/- 1.69 ng/mL; P <.05). Given a diagnosis of preterm labor, a TAT level of 8.0 ng/mL had a positive predictive value of 80% for delivery within 3 weeks of enrollment. CONCLUSIONS: This study showed that TAT levels are elevated in patients with preterm labor who are destined to deliver before term. These results suggest that preterm labor resulting in premature delivery is associated with the activation of thrombin. Future studies will further elucidate the role of thrombin in preterm parturition and confirm whether tests for thrombin activation can accurately identify those patients destined for preterm delivery.

Adult↗

PubMed2001

Effect of growth hormone treatment on testicular function, puberty, and adrenarche in boys with non-growth hormone-deficient short stature: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the effect of growth hormone (GH) therapy on pubertal onset, pubertal pace, adult testicular function, and adrenarche in boys with non-GH-deficient short stature. STUDY DESIGN: Randomized, double-blind, placebo-controlled trial. GH (0.074 mg/kg, subcutaneously, 3 times per week) or placebo treatment was initiated in prepubertal or early pubertal boys and continued until near final height was reached (n = 49). Statistical significance was assessed by survival analysis, repeated-measures analysis of variance, and Student t test. RESULTS: GH therapy did not affect the age at pubertal onset, defined either by testicular volume >4 mL or by testosterone concentration >1.0 nmol/L (30 ng/dL). GH treatment also did not affect the pace of puberty, defined either by the rate of change in testicular volume or testosterone concentration during the 4 years after pubertal onset. In boys followed up to age > or =16 years during the study, there were no significant differences in final testicular volume or in plasma testosterone, luteinizing hormone, or follicle-stimulating hormone concentrations. The pace of adrenarche, assessed by change in dehydroepiandrosterone sulfate levels over time, also did not differ significantly between the GH and placebo groups. CONCLUSION: Our findings suggest that GH treatment does not cause testicular damage, alter the onset or pace of puberty, or alter the pace of adrenarche in boys with non-GH-deficient short stature.

Adolescent↗

PubMed2001

Guidelines for counselling in infertility: outline version.

The Guidelines for Counselling in Infertility describe the purpose, objectives, typical issues and communication skills involved in providing psychosocial care to individuals using fertility services. The Guidelines are presented in six sections. The first section describes how infertility consultations differ from other medical consultations in obstetrics and gynaecology, whereas the second section addresses fundamental issues in counselling, such as what is counselling in infertility, who should counsel and who is likely to need counselling. Section 3 focuses on how to integrate patient-centred care and counselling into routine medical treatment and section 4 highlights some of the special situations which can provoke the need for counselling (e.g. facing the end of treatment, sexual problems). Section 5 deals exclusively with third party reproduction and the psychosocial implications of gamete donation, surrogacy and adoption for heterosexual and gay couples and single women without partners. The final section of the Guidelines is concerned with psychosocial services that can be used to supplement counselling services in fertility clinics: written psychosocial information, telephone counselling, self-help groups and professionally facilitated group work. This paper summarizes the different sections of the Guidelines and describes how to obtain the complete text of the Guidelines for Counselling in Infertility.

Counseling↗

PubMed2001

Catch-up growth is associated with delayed senescence of the growth plate in rabbits.

In mammals, release from growth-inhibiting conditions results in catch-up growth. To explain this phenomenon, we proposed the following model: 1) The normal senescent decline in growth plate function depends not on age per se, but on the cumulative number of replications that growth plate chondrocytes have undergone. 2) Conditions that suppress growth plate chondrocyte proliferation therefore slow senescence. 3) After transient growth inhibition, growth plates are thus less senescent and hence show a greater growth rate than expected for age, resulting in catch-up growth. To test this model, we administered dexamethasone to growing rabbits to suppress linear growth. After stopping dexamethasone, catch-up growth occurred. In distal femoral growth plates of untreated controls, we observed a senescent decline in the growth rate and in the heights of the proliferative zone, hypertrophic zone, and total growth plate. During the period of catch-up growth, in the animals previously treated with dexamethasone, the senescent decline in all these variables was delayed. Prior treatment with dexamethasone also delayed epiphyseal fusion. These findings support our model that linear catch-up growth is caused, at least in part, by a delay in growth plate senescence.

Animals↗

PubMed2001

Regulation of growth plate chondrogenesis by bone morphogenetic protein-2.

Bone morphogenetic proteins (BMPs) regulate embryonic skeletal development. We hypothesized that BMP-2, which is expressed in the growth plate, also regulates growth plate chondrogenesis and longitudinal bone growth. To test this hypothesis, fetal rat metatarsal bones were cultured for 3 days in the presence of recombinant human BMP-2. The addition of BMP-2 caused a concentration-dependent acceleration of metatarsal longitudinal growth. As the rate of longitudinal bone growth depends primarily on the rate of growth plate chondrogenesis, we studied each of its three major components. BMP-2 stimulated chondrocyte proliferation in the epiphyseal zone of the growth plate, as assessed by [(3)H]thymidine incorporation. BMP-2 also caused an increase in chondrocyte hypertrophy, as assessed by quantitative histology and enzyme histochemistry. A stimulatory effect on cartilage matrix synthesis, assessed by (35)SO(4) incorporation into glycosaminoglycans, was produced only by the highest concentration of BMP-2. These BMP-2-mediated stimulatory effects were reversed by recombinant human Noggin, a glycoprotein that blocks BMP-2 action. In the absence of exogenous BMP-2, Noggin inhibited metatarsal longitudinal growth, chondrocyte proliferation, and chondrocyte hypertrophy, which suggests that endogenous BMPs stimulate longitudinal bone growth and chondrogenesis. We conclude that BMP-2 accelerates longitudinal bone growth by stimulating growth plate chondrocyte proliferation and chondrocyte hypertrophy.

Animals↗

PubMed2000

Recruiting subjects in cancer prevention and control studies.

Recruitment of subjects is a critical aspect of prevention trials that is often overlooked by investigators. As a consequence, accrual time is often extended, workloads may become heavy, and resource utilization is increased in an effort to complete projects. Recruitment of healthy subjects in cancer prevention and control studies presents unique issues that need to be considered. The barriers to recruitment include participant issues, physician variables, features of the study design, and characteristics of the health care system in the United States. The authors provide their experience in overcoming these difficulties.

Case-Control Studies↗

PubMed2000

Catch-up growth: possible mechanisms.

Many systemic diseases impair linear growth. If remission occurs, growth will often accelerate beyond the normal rate for age, a phenomenon termed "catch-up growth." As a result, final height is improved, although this recovery of adult stature is frequently incomplete. Two principal models have been proposed to explain catch-up growth. The first model postulates a central nervous system mechanism that compares actual body size with an age-appropriate set-point and then adjusts growth rate accordingly. However, there is recent evidence that growth inhibition in a single growth plate is followed by local catch-up growth, a finding not readily explained by the neuroendocrine model. Thus, a new model has been proposed that places the mechanism within the growth plate itself. According to this model, growth-inhibiting conditions decrease proliferation of growth plate stem cells, thus conserving their proliferative potential. Additional research is needed to determine whether the mechanisms governing catch-up growth are local, systemic, or both.

Animals↗

PubMed2000

How serious are expressions of protected values?

People think that some things that they value should be protected from trade-offs with other things. For example, people think that no economic gain is great enough to justify clear-cutting old-growth forest. The authors probed the stability of these protected values (PVs) in several ways. Subjects were asked to think of counterexamples, and this had some effect on PVs. Subjects were then asked how they would resolve conflicts between 2 PVs. Resolutions did not differ from those between other values, but subjects tended to feel that conflicts between PVs did not occur in reality. Despite people's claims that PVs are unchanged by variation in quantity, expression of PVs was reduced when the magnitude or probability of the violation of a PV was smaller. In summary, PVs appear to be labile and amenable to challenge. Despite earlier concerns, apparent PVs may not always preclude the use of valuation measures in cost-effectiveness analysis or negotiated agreement on controversial issues.

Adolescent↗

PubMed2000

Birth outcome following maternal use of metoclopramide. The Euromap study group.

AIMS: Metoclopramide is an antiemetic drug used widely during pregnancy for nausea and vomiting. Because of its frequent use any adverse effects on infant health would have major public health implications. We therefore examined the safety of metoclopramide during pregnancy. METHODS: Using the Pharmaco-Epidemiological Prescription Database of North Jutland County, we identified 309 women with singleton pregnancies who had prescriptions for metoclopramide fom 1 January 1991 to 31 December 1996. Information on malformations, birth weight, preterm deliveries and stillbirth were compared with 13 327 references who did not receive prescriptions of any kind during pregnancy. RESULTS: Mean birth weight among exposed women was 3480 g compared with 3470 g among nonexposed. Based on logistic regression models no major differences in the risk were found concerning malformations (OR= 1.11; 95% confidence interval (CI): 0.6-2.1); low birth weight (OR= 1.79; 95% CI: 0.8-3.9) or preterm delivery (OR= 1.02; 95 CI: 0.6-1.7). CONCLUSIONS: We could not document any association between the use of metoclopramide during pregnancy and adverse pregnancy outcome. Because of the limited power of our study further research is required.

Adolescent↗

PubMed2000

Are preferences for equity over efficiency in health care allocation "all or nothing"?

BACKGROUND: In a previous study we showed that within a budget constraint, most people would rather offer a less effective screening test to 100% of a Medicaid population, thereby saving 1,000 lives, than a more effective test to 50% of the population, thereby saving 1,100 lives. We present here a study exploring whether this preference for equity over efficiency persists when neither test can be offered to the entire population. METHODS: Members of Physicians' Online and prospective jurors at the Philadelphia County Courthouse randomly received 1 of 3 questionnaires (Q1, Q2, or Q3) describing a limited budget to screen Medicaid enrollees for colon cancer. In all questionnaires, test 1 was said to save 1,000 lives, and test 2, a more effective and more expensive test, was said to save 1,100. In Q1, test 1 was offered to 100% and test 2 to 50% of the population. In Q2, the 2 tests could be offered to 50% and 25%, respectively; in Q3, to 90% and 40%, respectively. Respondents indicated which test they recommended and provided justification. RESULTS: The majority of physicians (59%) and the general public (56%) receiving Q1 favored the less effective screening test However, of those receiving Q2, only 26% of physicians and 27% of the general public recommended the less effective screening test. And of those receiving Q3, only 38% of physicians and 28% of the general public recommended the less effective test. Justifications for these recommendations were based largely on concerns for equality of treatment among those who chose the less effective test and concerns for saving the most lives among those who preferred the more effective test. CONCLUSIONS: Although most respondents show a preference for equity over efficiency when equity means that 100% of a population can receive a service, many fewer respondents maintain this preference when equity is no longer absolute. This result suggests that the preference for equity is sometimes "all or none."

Adult↗

PubMed2000

Determinants of priority for risk reduction: the role of worry.

One hundred twenty-two members (experts) of the Society for Risk Analysis completed a mailed questionnaire and 150 nonexperts completed a similar questionnaire on the World Wide Web. Questions asked included those about priorities on personal and government action for risk reduction, badness of the risk, number of people affected, worry, and probabilities for self and others. Individual differences in mean desire for action were largely explained in terms of worry. Worry, in turn, was largely affected by probability judgments, which were lower for experts than for nonexperts. Differences across risks in the desire for action, within each subject, were also determined largely by worry and probability. Belief in expert knowledge about the risk increased worry and the priority for risk reduction. A second study involving 91 nonexperts (42 interviewed and 49 on the Web) replicated the main findings for nonexperts from the first study. Interviews also probed the determinants of worry, attitudes toward government versus personal control, and protective behaviors.

Adolescent↗