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Biomedical subjects

R Schulz

Publications and source records attributed to R Schulz.

At least 217 records · Page 12Linked to original sources
PubMed1998

Phosducin expression in NG 108-15 hybrid cells enhances prostaglandin E1 stimulated adenylate cyclase activity.

Phosducin (Phd), a cytosolic protein, has been proposed to compete with certain receptor kinases for Gbetagamma of heterotrimeric G proteins, and may inhibit GTPase activity of G alpha s. These suggestions together with the enhancing effect of Phd on odorant-induced cAMP accumulation let us assume a stimulatory action of the protein on intracellular signaling. Therefore, this investigation was designed to examine the excitatory effect of PGE1 on signal transmission in neuroblastoma x glioma hybrid cells (NG 108-15) overexpressing Phd. The neuronal cells stably expressing Phd were found to display a 3 to 4-fold increased sensitivity to PGE1 as compared to wild type cells, using cAMP accumulation as measure. Examination of membranes prepared from Phd-overexpressing cells revealed an elevated GTPase activity as indicated by the formation of 32Pi upon PGE1 challenge. This activity was inhibited by exogenous Phd. In addition, receptor independent stimulation of adenylate cyclase by forskolin reveals an increased formation of cAMP in Phd expressing cells, which is accompanied by an increased binding of [3H]forskolin. The findings let us propose that Phd elevates intracellular levels of functional G alpha s which accounts for the increased response to PGE1.

Adenylyl Cyclases↗
PubMed1998

A qualitative field method for monitoring pesticides in the edge-of-field runoff.

A field method is described, which allows the qualitative estimation of pesticide contamination in the edge-of-field runoff. The method employs cheap and easy-to-use runoff sampling bottles, which were installed in an agricultural stream catchment over a period of three growing seasons. During this time 18 runoff events were detected, in nine of which insecticide contamination was measured (maximum concentrations: lindane 0.7 microgram l-1 and 12.7 micrograms kg-1, parathion 20 micrograms l-1 and 728 micrograms kg-1, fenvalerate 18.4 micrograms l-1 and 924 micrograms kg-1). These insecticides were detected mainly as particle-bound chemicals. On about 80% of the occasions the presence or absence of runoff measured in the field was in agreement with a simulation of runoff presence or absence using the runoff model KINEROS.

Agriculture↗
PubMed1998

Spousal caregivers' activity restriction and depression: a model for changes over time.

In this paper we examine the effects of increasing as well as decreasing caregiving demands on depressive symptomatology. In addition, we focus on spousal caregivers' activity restriction as an explanatory mechanism for changes in depressive symptomatology in the caregiving context. Two databases are used to answer our research questions. An increase of caregiving demands is assessed in study 1, which includes prospective data on 127 spousal caregivers of stroke, hip fracture, congestive heart failure and myocardial infarction patients. A decrease of caregiving demands is examined in study 2, which includes prospective data on 110 spousal caregivers of bypass operation patients. The results generally support the hypothesis that an increase in caregiving demands results in increased depressive symptomatology, while a decrease in caregiving demands reduces depressive symptomatology. The results also support the notion of activity restriction as a critical mediator of changes in depressive symptoms. Cross-sectionally it mediates the association between caregiving and depressive symptomatology, and longitudinally it contributes to changes in depressive symptomatology in both samples.

Activities of Daily Living↗
PubMed1998

Disinhibition in the gamma motoneuron circuitry: a neglected mechanism for understanding myofascial pain syndromes?

Dysregulation in the gamma motoneuron circuitry is proposed as one mechanism to explain the development of trigger point activity in myofascial pain syndrome. Dysregulation in this context is defined operationally as significantly (and functionally) different levels of electrical activity detected in the same muscle on the left and right sides of the body that is persistently present with movement of that muscle. Neurophysiological concepts as they pertain to muscles and motor control principles are reviewed. Research is integrated that ties together material from diverse fields of psychology and medicine. Dysregulation in the gamma motoneuron circuitry may lead to disinhibition of muscle that causes it to remain hyperactive after contraction, generate excessive electrical activity during movement, and/or inappropriately coactivate with other muscles during movement. Any or all of these phenomena may occur with dysregulation. Such dysregulation may be corrected by learning. Immediate clinical implications are discussed, including the addition of specifically targeted neuromuscular retraining procedures via surface electromyography, as well as some conceptual and research issues that require further clarification.

Facial Muscles↗
PubMed1998

Activity restriction and prior relationship history as contributors to mental health outcomes among middle-aged and older spousal caregivers.

In a sample of cancer patients (n = 75) and spousal caregivers (24 men and 51 women), restriction in caregiver routine activities mediated associations between caregiving stress (patient symptom severity) and caregiver depressed affect and resentment. Moreover, the antecedents and affective consequences of caregiver activity restriction were consistent with the theory of communal relationships (e.g., M. S. Clark & J. Mills, 1979, 1993). If a relationship had been communal in the past (i.e., characterized by mutual concern for and responsiveness to one another's needs), activity restriction was predicted by intimacy and affectional loss (rather than by the severity of patient symptoms) and in turn predicted caregiver depressed affect. Among caregivers in less communal relationships, activity restriction was predicted by severity of patient symptoms (rather than by intimacy and affectional loss) and in turn predicted resentment of care recipients and the caregiving role.

Adaptation, Psychological↗
PubMed1998

Caregiving from the recipient's perspective: negative reactions to being helped.

This study investigated predictors of negative reactions to assistance provided to a physically disabled spouse (n = 276, M age: 76.6 years) and the consequences that negative reactions may have for the mental health of the care recipient. Nearly 40% of recipients reported some emotional distress in response to help they received. Fatalistic attitudes, perceived control, and lower self-esteem predicted greater helping distress, whereas lower self-esteem, fatalistic beliefs, and marital conflict were especially likely to lead to helping distress for those who received higher levels of assistance. Helping distress was also found to predict depression as much as 1 year later, suggesting that there may be long-term consequences of negative reactions to assistance. These findings have important implications for the study of caregiving and the relationship between physical impairment and depression.

Activities of Daily Living↗
PubMed1998

K(ATP)-channel activation: effects on myocardial recovery from ischaemia and role in the cardioprotective response to adenosine A1-receptor stimulation.

1. Optimization of myocardial energy substrate metabolism improves the recovery of mechanical function of the post-ischaemic heart. This study investigated the role of K(ATP)-channels in the regulation of the metabolic and mechanical function of the aerobic and post-ischaemic heart by measuring the effects of the selective K(ATP)-channel activator, cromakalim, and the effects of the K(ATP)-channel antagonist, glibenclamide, in rat fatty acid perfused, working hearts in vitro. The role of K(ATP) channels in the cardioprotective actions of the adenosine A1-receptor agonist, N6-cyclohexyladenosine (CHA) was also investigated. 2. Myocardial glucose metabolism, mechanical function and efficiency were measured simultaneously in hearts perfused with modified Krebs-Henseleit solution containing 2.5 mM Ca2+, 11 mM glucose, 1.2 mM palmitate and 100 mu l(-1) insulin, and paced at 300 beats min(-1). Rates of glycolysis and glucose oxidation were measured from the quantitative production of 3H20 and 14CO2, respectively, from [5-3H/ U-14C]-glucose. 3. In hearts perfused under aerobic conditions, cromakalim (10 microM), CHA (0.5 microM) or glibenclamide (30 microM) had no effect on mechanical function. Cromakalim did not affect glycolysis or glucose oxidation, whereas glibenclamide significantly increased rates of glycolysis and proton production. CHA significantly reduced rates of glycolysis and proton production but had no effect on glucose oxidation. Glibenclamide did not alter CHA-induced inhibition of glycolysis and proton production. 4. In hearts reperfused for 30 min following 30 min of ischaemia, left ventricular minute work (LV work) recovered to 24% of aerobic baseline values. Cromakalim (10 microM), administered 5 min before ischaemia, had no significant effect on mechanical recovery or glucose metabolism. CHA (0.5 microM) significantly increased the recovery of LV work to 67% of aerobic baseline values and also significantly inhibited rates of glycolysis and proton production. Glibenclamide (30 microM) significantly depressed the recovery of mechanical function to < 1% of aerobic baseline values and stimulated glycolysis and proton production. 5. Despite the deleterious actions of glibenclamide per se in post-ischaemic hearts, the beneficial effects of CHA (0.5 microM) on the recovery of mechanical function and proton production were not affected by glibenclamide. 6. The data indicate that the cardioprotective mechanism of adenosine A1-receptor stimulation does not involve the activation of K(ATP)-channels. Furthermore, in rat fatty acid perfused, working hearts, stimulation of K(ATP)-channels is not cardioprotective and has no significant effects on myocardial glucose metabolism.

Adenosine↗
PubMed1998

The remission status before and the PCR status after high-dose therapy with peripheral blood stem cell support are prognostic factors for relapse-free survival in patients with follicular non-Hodgkin's lymphoma.

It was the aim of our study to examine the clinical significance of t(14;18)-positive cells in samples from 47 patients with follicular non-Hodgkin's lymphoma (NHL) who underwent high-dose therapy with autologous peripheral blood stem cell (PBSC) transplantation. At the time of PBSC mobilization, 25 patients were in first remission, while 22 patients had a history of previous treatment failure. At the same time, 43 patients had polymerase chain reaction (PCR)-positive cells in samples from bone marrow (BM) and/or peripheral blood (PB). Independent of the remission status, high-dose cytarabine and mitoxantrone with granulocyte colony-stimulating factor (G-CSF) support were administered for PBSC mobilization. Following high-dose conditioning therapy which consisted of cyclophosphamide (200 mg/kg) and hyperfractionated total body irradiation (TBI, 14.4 Gy) or BEAM (carmustine, etoposide, cytarabine, melphalan), 34 patients received PCR-positive and 13 patients received PCR-negative autografts. After a median follow-up time of 20 months (range, 6-50) post-transplantation, 33 patients were in remission, while 14 patients had relapsed after a median time of 14.5 months (range, 10-42). Using the Andersen-Gill proportional hazards regression model for the analysis of relapse-free survival, we found that PCR-positive findings in samples from BM and/or PB at any given time-point after transplantation were associated with an increased estimated hazard ratio of 4.5 in comparison with a PCR-negative finding (P=0.013). On the other hand, patients included while they were in first remission had a smaller estimated hazard ratio of 0.3 when compared with patients with a history of previous treatment failure (P=0.048). For the latter group of patients, this translates into a significantly smaller probability of relapse-free survival in comparison to patients who were in first remission at the time of PBSC-mobilization (P=0.012). In conclusion, the remission status of the patients before autografting and the PCR status as assessed on the occasion of follow-up examinations are significant prognostic parameters for relapse-free survival in patients with follicular lymphoma undergoing high-dose therapy with PBSC autografting.

Adult↗
PubMed1998

D alpha3, a new functional alpha subunit of nicotinic acetylcholine receptors from Drosophila.

Nicotinic acetylcholine (ACh) receptors (nAChRs) are important excitatory neurotransmitter receptors in the insect CNS. We have isolated and characterized the gene and the cDNA of a new nAChR subunit from Drosophila. The predicted mature nAChR protein consists of 773 amino acid residues and has the structural features of an ACh-binding alpha subunit. It was therefore named D alpha3, for Drosophila alpha-subunit 3. The d alpha3 gene maps to the X chromosome at position 7E. The properties of the D alpha3 protein were assessed by expression in Xenopus oocytes. D alpha3 did not form functional receptors on its own or in combination with any Drosophila beta-type nAChR subunit. Nondesensitizing ACh-evoked inward currents were observed when D alpha3 was coexpressed with the chick beta2 subunit. Half-maximal responses were at approximately 0.15 microM ACh with a Hill coefficient of approximately 1.5. The snake venom component alpha-bungarotoxin (100 nM) efficiently but reversibly blocked D alpha3/beta2 receptors, suggesting that D alpha3 may be a component of one of the previously described two classes of toxin binding sites in the Drosophila CNS.

Amino Acid Sequence↗
PubMed1998

Correlates and prevalence of benzodiazepine use in community-dwelling elderly.

OBJECTIVE: To describe the prevalence of benzodiazepine use, sociodemographic and physical health factors associated with use, dosages taken, and directions for use among individuals aged 65 years and older. DESIGN: Cross-sectional analysis of baseline data from the community-based, prospective observational Cardiovascular Health Study. PATIENTS/PARTICIPANTS: Medicare eligibility lists from four U.S. communities were used to recruit a representative sample of 5,201 community-dwelling elderly, of which 5,181 participants met all study criteria. MEASUREMENTS AND MAIN RESULTS: Among participants, 511 (9.9%) were taking at least one benzodiazepine, primarily anxiolytics (73%). Benzodiazepines were often prescribed to be taken pro re nata (PRN "as needed"), and 36.5% of prescriptions with instructions to be taken regularly were taken at a dose lower than prescribed. Reported over-the-counter (OTC) sleep aid medication use was 39.2% in benzodiazepine users and 3.3% in nonusers. In a multivariate logistic model, the significant independent correlates of benzodiazepine use were being white (odds ratio [OR] 1.9; 95% confidence interval [CI] 1.0, 3.4), female (OR 1.7; CI 1.4, 2.2), and living in Forsyth County, North Carolina, or Washington County, Maryland, compared with living in Sacramento County, California, or Allegheny County, Pennsylvania (OR 2.3; CI 1.4, 2.2); having coronary heart disease (OR 1.6; CI 1.2, 2.1), health status reported as poor or fair (OR 1.8; CI 1.4, 2.3), self-reported diagnosis of nervous or emotional disorder (OR 6.7; CI 5.1, 8.7), and reporting use of an OTC sleep aid medication (OR 18.7; CI 14.1, 24.7). CONCLUSIONS: One in 10 participants reported taking a benzodiazepine, most frequently an anxiolytic, often at a lower dose than prescribed and usually PRN. The high prevalence of OTC sleep aid medication and benzodiazepine use may place the patient at increased risk of psychomotor impairment. Physicians should assess OTC sleep aid medication use when prescribing benzodiazepines.

Aged↗
PubMed1998

Pathophysiology of hibernation, stunning, and ischemic preconditioning.

Analyses of regional myocardial blood flow, function, metabolism, and morphology in ischemic and reperfused myocardium has led to the identification of important phenomena, i.e. myocardial hibernation, myocardial stunning, and ischemic preconditioning. Hibernation is a condition of sustained reduction of contractile function in hypoperfused but viable myocardium, which improves upon reperfusion. Stunning is characterized by spontaneously reversible postischemic dysfunction despite completely restored perfusion. Ischemic preconditioning refers to a delay of myocardial infarction resulting from sustained ischemia, when the myocardium is subjected to one or more preceding short cycles of ischemia/reperfusion. Whereas stunning is a reversible manifestation of myocardial injury, hibernation and ischemic preconditioning are forms of endogenous myocardial protection against ischemia. With better understanding of the underlying mechanisms of hibernation and ischemic preconditioning, these mechanisms might be exploited for pharmacological cardioprotection.

Animals↗
PubMed1998

Functional outcome assessment of adults with right hemisphere brain damage.

This article addresses functional outcome assessment of adults with cognitive-communicative disorders due to relatively focal right hemisphere brain damage (RBD). Our discussion observes the World Health Organization's orientation on the multidimensional consequences of health conditions. The WHO framework distinguishes specific deficits (impairments) from their functional consequences: disabilities, or restrictions in daily life activities and handicaps, or broader changes in life role participation. Although there is little evidence about the functional aftermath of RBD, especially in relation to cognitive-communicative disorders, we summarize the data and observations that are available and hypothesize about relationships among outcomes at different levels. We also describe some tools and procedures that may be useful for measuring functional outcomes after RBD, along with relevant caveats, and end with a discussion of research needs and future directions, emphasizing gaps that span the range from basic investigation to treatment research to instrument and procedure development.

Adult↗
PubMed1998

The role of neuroticism and mastery in spouse caregivers' assessment of and response to a contextual stressor.

Data from more than 300 spousal caregivers and their care recipients were analyzed to demonstrate the effects of caregivers' personality attributes--neuroticism and mastery--on their assessment of a contextual stressor (the care recipient's behavioral and functional impairment) and on their experience of distress associated with that stressor. Caregivers who were high in neuroticism and/or low in mastery reported higher levels of behavioral and functional impairment in their disabled spouse and experienced more strain and depressive symptoms associated with caregiving relative to caregivers with lower neuroticism or higher mastery scores. We further showed that the widely reported association between caregiver-assessed impairment of the care recipient and caregiver outcomes can in part be explained by caregivers' personality attributes, such as neuroticism and mastery. Our findings that caregivers' personality variables are related to their assessment of a given objective stressor and their response to a given level of stress have implications for interventions targeting caregivers and for the use of caregivers as proxy informants.

Aged↗
PubMed1998

Intrinsic ANG II type 1 receptor stimulation contributes to recovery of postischemic mechanical function.

To determine whether intrinsic angiotensin II (ANG II) type 1 receptor (AT1-R) stimulation modulates recovery of postischemic mechanical function, we studied the effects of selective AT1-R blockade with losartan on proton production from glucose metabolism and recovery of function in isolated working rat hearts perfused with Krebs-Henseleit buffer containing palmitate, glucose, and insulin. Aerobic perfusion (50 min) was followed by global, no-flow ischemia (30 min) and reperfusion (30 min) in the presence (n = 10) or absence (n = 14) of losartan (1 mumol/l) or the cardioprotective adenosine A1 receptor agonist N6-cyclohexyladenosine (CHA, 0.5 mumol/l, n = 11). During reperfusion in untreated hearts (controls), left ventricular (LV) minute work partially recovered to 38% of aerobic baseline, whereas proton production increased to 155%. Compared with controls, CHA improved recovery of LV work to 79% and reduced proton production to 44%. Losartan depressed recovery of LV work to 0% without altering proton production. However, exogenous ANG II (1-100 nmol/l) in combination with losartan restored recovery of LV work during reperfusion in a concentration-dependent manner, suggesting that postischemic recovery of function depends on intrinsic AT1-R stimulation.

Angiotensin II↗
PubMed1998

Proinflammatory cytokines depress cardiac efficiency by a nitric oxide-dependent mechanism.

Proinflammatory cytokines (interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma; Cytomix) depress myocardial contractile work partially by stimulating expression of inducible nitric oxide (NO) synthase (iNOS). Because NO and peroxynitrite inhibit myocardial O2 consumption (MVO2), we examined whether this mechanism contributes to reduced cardiac work. In control isolated working rat hearts, cardiac work was stable for 60 min, followed by a decline from 60 to 120 min, without change in MVO2. Cardiac efficiency (work/MVO2) was therefore reduced from 60 to 120 min. Cytomix shortened the onset (within 20-40 min) and enhanced the depression in cardiac work and efficiency and inhibited MVO2 after 80 min. Mercaptoethylguanidine (MEG), an iNOS inhibitor and peroxynitrite scavenger, or the glucocorticoid dexamethasone (Dex) abolished the effects of Cytomix. iNOS expression was increased 10-fold by Cytomix and abolished by Dex but not MEG. That cytokine-induced depression in cardiac work precedes the reduction in MVO2 suggests, at least in the early response, that NO and/or peroxynitrite may not impair heart function by inhibiting mitochondrial respiration but reduce the heart's ability to utilize ATP for contractile work.

Animals↗
PubMed1998

Endothelial nitric oxide synthase increases in left atria of dogs with pacing-induced heart failure.

In congestive heart failure (CHF) the alterations in cardiac NO synthase (NOS) isoforms activity and expression are incompletely documented and the chamber specificity of these changes is unknown. We studied plasma nitrate-nitrite (NO-x), atrial, and ventricular NOS activities and protein expression (Western blot and densitometric analysis) in nonpaced control dogs and in dogs paced for 2 or 21 days into CHF. Plasma NO-x rose significantly after 7 and 21 days of pacing, whereas creatinine levels remained unchanged. In control dogs Ca2+-dependent NOS activity in left atria was double that of right or left ventricular activity. In paced animals the activity increased only in the atria after 21 but not 2 days of pacing. Levels of endothelial NOS (eNOS) protein were enhanced in the left atria but not ventricles after 21 days of pacing because of a greater quantity of the 150-kDa but not the 135-kDa eNOS. Ca2+-independent NOS activity was undetectable in any cardiac tissue. The specific upregulation of eNOS in the left atria suggests that NO production may be enhanced to counterbalance hypertrophy that develops during pacing-induced CHF.

Animals↗
PubMed1998

Characteristics and course of major depression in older primary care patients.

OBJECTIVE: Identify the morbidity patterns displayed by older primary care patients experiencing depressive symptomatology who do and do not meet criteria for a major depression. METHOD: Patients ages sixty and older presenting at two ambulatory internal medicine centers were administered the CES-D. Among those scoring > or = 11, 104 completed a comprehensive assessment of their psychiatric symptomatology, medical illness, and functional abilities. The assessment battery was again administered six months later. RESULTS: The point prevalence of major depression in older primary care patients is estimated at 9 percent based on SCID interviews. Patients meeting criteria for this diagnosis compared to those who are symptomatic but not experiencing a major depression described more extensive psychopathology but also significantly more limitations in performing social and functional roles. At six-month follow-up, only 11.5 percent of those initially diagnosed with a major depression were considered fully recovered. CONCLUSIONS: Major depression is a prevalent disorder in older primary care patients which affects their ability to perform expected social and physical roles. Mechanisms for delivering efficacious treatments in routine medical practice are of a high priority.

Age Factors↗