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Biomedical subjects

H G Schneider

Publications and source records attributed to H G Schneider.

At least 19 recordsLinked to original sources

Influence of atrial fibrillation on cardiac brain natriuretic peptide release during haemodynamic stress in heart failure.

BACKGROUND: The determinants of release of brain natriuretic peptide (BNP) in heart failure (HF) are incompletely understood, particularly, the effect of heart rhythm and haemodynamic stress. AIMS: To investigate the effect of haemodynamic stress on cardiac BNP release in HF and differentiate this response for atrial fibrillation (AF) and sinus rhythm (SR). METHODS: In 18 HF patients (ejection fraction<40%, 9 in AF and 9 in SR) haemodynamics and BNP levels were measured from arterial and coronary sinus samples at baseline, after 10 min of 20 degrees passive head up tilt (HUT) and after 10 min of isometric handgrip (IHG) exercise. From these data, we calculated a transcardiac BNP gradient and compared results between the AF and SR cohort. RESULTS: During haemodynamic stress in both groups, there were no significance differences in left sided filling pressures. At baseline, there were no differences in BNP measurements between the SR and AF group. The transcardiac BNP gradient increased significantly in the SR (p=0.02) but not the AF cohort, after HUT. During IHG exercise, there was a significant decrease in cardiac BNP release in the AF cohort (p=0.03) but not the SR cohort. CONCLUSION: These data imply in HF, cardiac rhythm influences cardiac BNP release in response to haemodynamic stress.

Aged↗

Anger expression: parental and cognitive factors.

The associations of parental moral disengagement, guilt, prosocial behavior, and anger, with their children's maladaptive anger was examined. 98 college undergraduate students and their parents participated. Both students and parents completed the Anger Response Inventory, the Mechanism of Moral Disengagement Scale, the Texas Social Behavior Inventory, the Fear of Punishment Scale, and the Need for Reparation Scale. A multiple regression analysis was performed to assess the students' variables which predicted maladaptive anger. Only moral disengagement was a predictor of the students' maladaptive anger. Subsequent multiple regression analyses were used to examine whether parental variables predict students' anger. Fathers' maladaptive anger, and prosocial skills were significantly related to students' maladaptive anger. Maternal variables produced an increase in the multiple R similar to the fathers', but none of the individual measures were significantly associated with the students' maladaptive anger.

Adaptation, Psychological↗

Measurement of cardiac troponin I levels in the emergency department: predictive value for cardiac and all-cause mortality.

OBJECTIVE: To assess the predictive value of cardiac troponin I levels in cardiac and all-cause mortality in patients presenting to an emergency department. DESIGN: A prospective cohort study. SETTING: The emergency department of a major tertiary teaching hospital in metropolitan Melbourne over a six-week period in 1998. PATIENTS: All patients with requests for cardiac enzyme level measurement. MAIN OUTCOME MEASURES: Cardiac and all-cause mortality within 30 days of presentation. RESULTS: 424 patients (232 men, 192 women; age range, 16-93 years) were reviewed. The 30-day mortality rate was 7.3% (31/424); in patients with raised levels of both creatine kinase (CK)-MB isoenzyme and troponin I this rate was 27% (7/26; 95% CI, 13%-44%); and in those with troponin I levels above 2 microg/L, but normal CK-MB values, it was 24% (5/21; 95% CI, 5%-43%). The mortality rate in the group with normal results of cardiac markers was 4.3% (14/328; 95% CI, 2.1%-6.5%). Patients with minor increases in troponin I levels (minimal myocardial damage) showed an intermediate 30-day mortality rate (13%, 5/39; 95% CI, 2%-24%). Other predictors of 30-day mortality included age, presentation with shortness of breath, and electrocardiography (ECG) changes diagnostic of acute myocardial infarction or consistent with ischaemia. Cardiovascular causes were responsible for most of the deaths in patients with raised troponin I levels. Multivariate logistic regression analysis showed that raised levels of troponin (> 2.0 microg/L), but not of CK-MB, predict 30-day mortality rate. CONCLUSIONS: Compared with CK-MB, cardiac troponin I more accurately predicts 30-day mortality rates in patients presenting to the emergency department. Moreover, troponin I levels identify additional groups of patients at increased risk of death not so identified by measuring CK-MB values.

Adolescent↗

Provision of laboratory services for heart and lung transplantation in Australia.

BACKGROUND: Laboratory services for the support of heart and lung transplantation in Australia have adapted to the special needs of the clinicians looking after the heart and lung transplantation patients. METHODS: Pre-transplantation standardized tests encompassing a wide variety of different parameters are carried out both to establish the suitability of patients for a transplant and to maximize the chance of success following this procedure. Potential solid organ recipients routinely have blood samples sent to a number of centers Australia-wide so that human leukocyte antigen (HLA) presensitization can be checked for at the time a donor becomes available in any state in Australia. Although prospective HLA matching is not performed for thoracic organ transplant recipients, pre-existing antibodies to donor HLA antigens are a contra-indication to transplantation. Following transplantation, the predominant roles of the laboratory are in the monitoring of immunosuppressive drug levels, in the detection of allograft rejection, and in the detection of bacterial infection or viral reactivation. While a number of markers have been proposed in the detection of rejection, we currently rely on interpretation of the histological analysis of biopsies. The treatment with immune suppressive agents, in particular cyclosporin A, has made organ transplantation from non-HLA identical donors possible. As cyclosporin A and other immune suppressive drugs have significant side effects, their concentrations need to be carefully followed to guarantee sufficient immune suppression while avoiding renal failure and other complications including excessive immunosuppression and infectious disease risk. Recently, the role of viral reactivation with the human cytomegalovirus (HCMV) has attained more prominence. HCMV is a potential pathogen in up to 90% of thoracic organ transplant recipients and in the pre-gancyclovir era, it was a major cause of morbidity and mortality in at-risk lung transplant recipients. New PCR-based assays that measure the viral load levels of HCMV allow earlier intervention and more appropriate treatment strategies to prevent the HCMV disease syndromes and optimize the HCMV prophylaxis strategy. CONCLUSIONS: Diagnostic pathology testing to support heart and lung transplantation is a combination of routine testing and specialized testing. Depending on the time-critical nature of the tests, this testing has to be done on site or in more centralized testing facilities. Further developments in the laboratory support of heart and lung transplantation will hopefully continue to improve both the short- and long-term outcomes of thoracic organ transplant recipients.

Australia↗

Reversibility of histological and immunohistological abnormalities in sublabial salivary gland biopsy specimens following treatment with corticosteroids in Sjögren's syndrome.

Sjögren's syndrome (SS) is a chronic autoimmune disease characterised by specific lesions in exocrine glands, so sublabial minor salivary gland biopsy (SLGB) plays an important part in its diagnosis. The extent and composition of the lymphocytic infiltrate in SLGB specimens can be considered as target organ specific parameters. They are quantified after histological and immunohistological examination by a focus score (describing the extent of the infiltrate) and IgA% score (describing the composition of the infiltrate), respectively. However, little is known about the factors that contribute to the extent and composition of the infiltrate and whether these features are reversible as repeated SLGBs are rarely performed. A patient with SS is described who underwent SLGBs before and after treatment with high dose corticosteroids. After treatment there was not only clinical improvement, but also improvement in the histological and immunohistological parameters. Although these findings need to be confirmed in further studies, this suggests that histopathological changes may be reversible in SS. Furthermore, it shows that the potential effects of corticosteroid use should be taken into account when interpreting SLGB specimens. When clinical changes do parallel histological changes, repeated SLGBs might offer a marker for disease activity in patients with SS.

Adult↗

Test of parenting skills.

An item pool was developed to assess basic parenting skills in the areas of attachment, emotional capacity, judgment, knowledge of child development, and safety. Initially, 200 items were generated and completed by a sample of 15 parents. Item scores correlated with scores on a social desirability scale or having low variance were edited or eliminated. A sample of 56 parents completed the revised scale, a social desirability scale, and the Adult-Adolescent Parenting Inventory. The reliabilities of the final subscales of the Test of Parenting Skills were modest, ranging from .56 to .77. Scores on the subscales were also correlated with those subscales from the Adult-Adolescent Parenting Inventory. With the exception of the Judgment scores being correlated with the use of harsh discipline, the significant correlations suggested concurrent validity. The individual subscales require additional refinement to achieve adequate internal consistency, but they have potential for measuring competency in core parenting skills.

Adolescent↗

Parathyroid hormone-related protein mRNA and protein expression in multiple myeloma: a case report.

Multiple myeloma frequently leads to complications, such as osteolytic lesions, hypercalcemia, and pathological fractures. Increased bone resorption in myeloma is due to osteoclast activation. The nature of the osteoclast activator(s) remains unclear. We describe a case of multiple myeloma with marked hypercalcemia and skeletal complications that progressed rapidly despite chemotherapy. The patient had marked hypercalcemia at diagnosis (4.5 mmol/l), and elevated parathyroid hormone-related protein (PTHrP) levels were found in plasma. Analysis of the bone marrow trephine biopsy showed PTHrP gene transcription and protein in myeloma cells. These results provide strong evidence for the production of significant amounts of PTHrP by human myeloma cells. PTHrP has been measured as elevated in the plasma of patients with myeloma and might be an important contributor to the skeletal complications in this disease.

Aged↗

Feedback, test anxiety and performance in a college course.

The effects of three forms of test feedback and text anxiety on test performance were examined within the context of a self-paced, criterion-based course in educational psychology. 73 undergraduate students completed seven units of work and were evaluated by computer-administered unit tests. Students were randomly assigned to one of three test feedback forms: (1) item-by-item knowledge of responses, (2) answer-until-correct, and (3) delayed feedback. Students received their assigned feedback during the first two units, after which they were allowed to choose. Test anxiety was measured prior to testing on Sarason's Test Anxiety Scale and during testing on an item administered by the computer program. Students who reported high test anxiety on the Test Anxiety Scale experienced more anxiety during testing than students reporting low test anxiety. Anxiety during testing was not related to type of feedback, and the two variables were not related to course performance on the second unit. Data collected at the conclusion of the semester indicated that students who reported higher test anxiety required more attempts to pass unit tests than those reporting lower test anxiety. Given a choice, students preferred answer-until-correct feedback. This preference was not related to Test Anxiety Scale scores. Anxiety during testing was not related to being allowed to choose forms of feedback.

Achievement↗

Initial evidence for reliability and validity of a brief screening inventory for personality traits.

A short inventory was developed to screen for avoidant, borderline, and dependent personality disorders in clinic settings. The Personality Concerns Inventory items, adapted from the DSM-IV criteria for these disorders, along with the Millon-III was administered to 86 undergraduate students. Reliability estimates for the three scales were .87, .81, and .80. Scores on the three scales also correlated .49 to .57 with scores on the Avoidant, Borderline, and Dependent scales of the Millon-III.

Adolescent↗

Habit-specific locus of control scales for drinking, smoking, and eating.

The internal consistencies of three habit-specific locus of control scales measuring drinking, smoking, and eating behavior were evaluated using coefficient alpha. The three scales, along with Rotter's 1-E scale, were administered to 202 undergraduate students. Estimates indicated the scales showed reasonably high internal consistency. Scores on the smoking and drinking scales had the lowest correlations with scores on Rotter's generalized measure. Mean drinking scale scores were lower than those for smoking and eating, suggesting that people judge drinking to be under more personal control. The implications of habit-specific expectancies, particularly with regard to habit disorders, are discussed.

Adolescent↗

Homologous desensitization of calcitonin receptors and calcitonin-dependent adenylate cyclase in T47D cells.

Prolonged use of calcitonin (CT) in vivo leads to a loss of biological response (escape). To understand the molecular basis of this phenomenon, we examined desensitization of calcitonin receptors and down-regulation of adenylate cyclase response to CT in T47CD cells after a preincubation with CT. Preincubation with salmon or human CT (sCT, hCT) for 3 h led to a concentration-dependent loss of [125I]-sCT binding and a similar loss of adenylate cyclase response to a maximal stimulatory dose of sCT. At the same time there was an increased basal activity of the adenylate cyclase. After 24 h preincubation with sCT, basal cAMP levels fell considerably but not to basal levels. Time course experiments showed a delayed decline of maximally sCT-stimulated cAMP levels, which started after 1 h, while binding values declined over the first 60 min to one-third of the original values. Upon removal of CT from the medium, recovery of hormone binding occurred in parallel with the recovery of the adenylate cyclase response to sCT. T47D cells incubated with 25 mumol/l monensin, a lysosomal inhibitor, showed a persistent [125I]-sCT binding after removal of hormone, consistent with diminished intracellular receptor degradation. However, despite persistent binding to the cells, basal and stimulated cAMP levels dropped in the same manner as seen in controls. Our experiments support the view that tight binding of CT to its receptor stimulates adenylate cyclase in T47D cells, until receptors are removed by internalization. The physiological role of internalization of the CT receptor might be to end continuous stimulation of the adenylate cyclase, which occurs after binding.

Adenylyl Cyclases↗

A new in vitro bioassay for human calcitonin: validation and comparison to the rat hypocalcemia bioassay.

The human breast cancer cell line T 47 D expresses calcitonin (CT) receptors that are coupled to adenylate cyclase and which reveal a dose-dependent cyclic AMP response to CT. We used this model to establish an in vitro bioassay for synthetic human CT (hCT) preparations to overcome some of the obstacles of the standard rat hypocalcemia in vivo bioassay. The detection limit of the in vitro bioassay was 1 x 10(-10) M hCT (EC 50: 8.7 pM +/- 26%) compared to 7.3 x 10(-9) M (EC 50: 7.2 microM +/- 32%) for the in vivo bioassay. The relative potencies of test preparations revealed a good correlation (r = 0.89) and several hCT-related substances produced comparable results when tested by the two methods. The standard deviations of precision and accuracy, however, were significantly smaller (P less than 0.05) for the in vitro bioassay. According to these data the T 47 D in vitro bioassay is more sensitive, superior in precision and accuracy, and comparable in specificity to the rat hypocalcemia bioassay.

Adenylyl Cyclases↗

Transforming growth factor-beta modulates receptor binding of calciotropic hormones and G protein-mediated adenylate cyclase responses in osteoblast-like cells.

Transforming growth factor-beta (TGF beta) produced by osteoblasts is present in high levels in bone and influences bone formation, replication of bone cells, and expression of osteoblast protein products. Interactions between bone active hormones and locally released and activated TGF beta were studied by examining the influence of TGF beta preincubation on PTH, calcitonin (CT), and vitamin D receptors in an osteoblastic cell line (UMR 106-06). Preincubation of UMR 106-06 cells with 1 ng/ml TGF beta for 3 days increased specific binding of [125I]PTH-related protein (PTHrP)(1-84) to 140% of that in control cells, but [125I]salmon CT binding decreased to 50% of controls. Binding isotherms indicated that the changes in binding were due to altered receptor numbers since affinities for 125I-labeled PTH and CT remained unchanged. The effect on receptor levels was time dependent, requiring 24 h preincubation with TGF beta for measurable changes, and dose dependent, with maximal effects seen with 1 ng/ml TGF beta. Binding of [3H]1,25(OH)2 vitamin D3 was increased to 130% of control in cytosolic extracts of UMR 106-06 cells pretreated for 3 days with 1 ng/ml TGF beta. Scatchard plots suggested an increase in receptor number without change in affinity. The adenylate cyclase response to PTH increased to 150% of control cells after 3 days of treatment with 1 ng/ml TGF beta; however, the adenylate cyclase response to CT was little changed. Forskolin- and cholera toxin-stimulated adenylate cyclase responses were increased by TGF beta treatment to 130-160% of control, indicating an increase in the stimulatory subunit of the G protein. Increased abundance of both Gs and Gi proteins were indicated by increased cholera toxin- or pertussis toxin-dependent [32P] NAD ribosylation of 47-kilodalton (kDa) and 42-kDa or 40-kDa proteins, respectively, in TGF beta-treated cells. Our data support a complex regulatory effect of TGF beta on UMR 106-06 cells with increases in PTH receptors, vitamin D receptors, and G proteins, whereas there is an apparent down-regulation of CT receptors. TGF beta might induce a more differentiated osteoblast phenotype of these cells, which already express differentiated features such as high alkaline phosphatase activity, PTH and vitamin D receptors, and collagenase production. Since low doses of PTH stimulate bone formation in vivo, TGF beta released or activated at sites of new bone formation might locally modulate PTH activity be allowing increased PTH receptor and postreceptor effectiveness.

Adenylyl Cyclases↗

Specific down-regulation of parathyroid hormone (PTH) receptors and responses to PTH by tumour necrosis factor alpha and retinoic acid in UMR 106-06 osteoblast-like osteosarcoma cells.

Parathyroid hormone (PTH) and PTH-related protein (PTHrP) act via PTH receptors in bone to stimulate bone resorption. Bone resorption is also stimulated by certain cytokines, which are produced in bone and bone marrow. The effects of such cytokines on the PTH-receptor system were studied in the osteoblast-like osteosarcoma cell line UMR 106-06. 125I-labelled PTHrP-(1-84)-peptide bound specifically to the cells, and PTHrP-(1-34) and -(1-84) competed with equimolar affinity for binding to UMR 106-06 cells. The specific binding of 125I-PTHrP-(1-84) could be completely blocked by PTH. Therefore 125I-PTHrP-(1-84) bound to a classical receptor in UMR 106-06 cells. Preincubation for 3 days with either tumour necrosis factor alpha (TNF alpha) or retinoic acid (RA) both decreased the specific binding of 125I-PTHrP-(1-84) to about 40% of control levels. These effects were specific for PTH binding, since there was little effect on 125I-salmon-calcitonin binding. Both TNF alpha and RA required 24 h exposure to cells to produce a measurable effect. The decrease in 125I-PTHrP-(1-84) binding was due to a reduced number of binding sites, with little apparent change in affinity. Half-maximal effects were seen with 1 ng of TNF alpha/ml, whereas 1 microM-RA was needed to observe the loss of PTH receptors. Combinations of RA and TNF alpha produced a greater effect than that of either agonist alone. The loss of PTH receptors was accompanied by a specific loss of PTH-stimulated cyclic AMP production. Preincubation with TNF alpha increased the basal plasminogen activator (PA) activity in the cells and decreased the amplitude of the response of PA activity to PTH compared with control cells. Furthermore TNF alpha decreased sensitivity to PTH (50% stimulation of PA activity with 0.1 nM-PTH in control cells versus 50% stimulation with 0.3 nM-PTH in TNF alpha-treated cells). In contrast, TNF alpha pretreatment increased the amplitude of the response of PA activity to calcitonin, whereas sensitivity to calcitonin was not altered. These data are consistent with a specific down-regulation of PTH receptors in osteoblast-like UMR 106-06 cells after exposure to TNF alpha or RA. The loss of PTH receptors is accompanied by a decreased responsiveness to PTH, as measured with the PA system in these cells. A loss of PTH receptors could modulate PTH responses in osteoblasts, either in the local control of bone formation and resorption, or in pathological conditions such as humoral hypercalcaemia of malignancy.

Binding, Competitive↗

Reversible calcitonin binding to solubilized sheep brain binding sites.

In this study we have solubilized and characterized binding sites for calcitonin (CT) from sheep brainstem. Autoradiography of 125I-labelled salmon CT (125I-sCT) binding to sheep diencephalon revealed a similar pattern of binding to that seen in other species, although the extent of distribution was greater in the sheep. CT binding activity could be extracted from membranes with either CHAPS or digitonin, but not with beta-octyl glucoside, 125I-sCT binding was saturable, with a dissociation constant for CHAPS-solubilized membranes of 2.8 +/- 0.5 nM and a maximum binding site concentration of 6.2 +/- 1.6 pmol/mg of protein. In competition binding studies, various CTs and their analogues demonstrated a similar rank order of potency to that seen in other CT receptor systems, Optimal binding occurred in the pH range 6.5-7.5, and was decreased in the presence of NaCl concentrations greater than 200 mM. In contrast with most other CT receptor binding systems, in which binding is poorly reversible, the binding of 125I-sCT to sheep brain binding sites underwent substantial dissociation upon addition of excess unlabelled sCT, with 40% and 46% dissociation after 2 h at 4 degree C in particulate and solubilized membranes respectively. Photoaffinity labelling of the binding site with the biologically active analogue 125I-[Arg11,18,4-azidobenzoyl-Lys14]sCT and analysis on SDS/PAGE under reducing conditions revealed a specific protein band of Mr approximately solubilized and particulate brain membranes. This is in accordance with the molecular size of CT receptors in other tissues where two species of receptor have been identified. one of Mr approximately 71,000 and another of Mr approximately 88,000. These results demonstrate the presence of high concentrations of CT binding sites in sheep brain which display different kinetic properties to those of CT receptors found in other tissues.

Affinity Labels↗

Structural requirements for the action of parathyroid hormone-related protein (PTHrP) on bone resorption by isolated osteoclasts.

Parathyroid hormone-related protein (PTHrP) plays a major role in the syndrome of humoral hypercalcemia of malignancy (HHM) by its actions on bone and kidney. In this study an isolated osteoclast bone resorption assay was used to investigate the actions of this peptide and the structure-activity relationships for its resorption effect. As with PTH, neither synthetic nor recombinant PTHrP preparations stimulated resorption within highly purified osteoclast populations. Resorption was stimulated only in the presence of contaminating osteoblasts or in cocultures with the osteoblast-like cell line UMR-106. In the presence of osteoblasts PTHrP-(1-34) and PTHrP-(1-84) stimulated bone resorption in a dose-dependent manner with a potency comparable to that of PTH-(1-34) on a molar basis. The biologic activity of the PTHrP was shown to reside in the first 34 amino acids, and within that region the structural requirements for promotion of osteoclastic resorption resembled closely those for promotion of cyclic AMP formation in osteoblast-like cells. Using emulsion autoradiography with iodinated PTHrP-(1-34) and PTHrP-(1-84) on mixed bone cell preparations from neonatal rats, specific binding was demonstrated only to osteoblasts, not to osteoclasts. These results clearly demonstrate that PTHrP is a potent stimulator of bone resorption and that these effects are, like those of PTH, mediated by initial actions upon cells of the osteoblast lineage.

Animals↗