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Biomedical subjects

C Schroeder

Publications and source records attributed to C Schroeder.

At least 37 records · Page 2Linked to original sources

Clinical experience with minimally invasive coronary artery and mitral valve surgery with the advantage of cardiopulmonary bypass and cardioplegic arrest using the Port Access technique.

To minimize surgical trauma, the use of Port Access cardiac surgery was initiated in patients (pts) with coronary artery disease (CAD) (42 pts) or mitral valve disease (MVD) (24 pts) in March 1996 at our institution. Altogether 42 pts (36 men, 6 women; age 31-75 years, median 59.0 years) with isolated lesions of the left anterior descending (LAD) artery underwent Port Access coronary artery surgery (PACAS). A small (5-9 cm) incision was done parasternally on top on the fourth rib. The left internal mammary artery (LIMA) was dissected through the minithoracotomy or by using an additional thoracoscopic approach. A total of 24 pts (12 men, 12 women; age 30-75 years, median 62 years) underwent Port Access mitral valve surgery (PAMVS). In these pts the procedure was performed through a small right thoracotomy (6-8 cm). In all cases, endovascular cardiopulmonary bypass (CPB) was instituted through femoral cannulation, and an additional endoaortic balloon catheter was introduced into the ascending aorta for aortic occlusion. In pts with PACAS the survival was 98% (41/42) and in the PAMVS group 100%. All pts but one survived the PACAS and are well today. There were no deaths in the PAMVS group. The hospital stay was reduced by 1 day on average after PACAS and 3 days after PAMVS. Thus in well selected patients Port Access cardiac surgery represents a safe and feasible minimally invasive surgical approach that avoids the potential complications of a sternotomy while offering the advantages and safety of CPB and cardioplegic arrest. This minimally invasive approach offers a shortened hospital stay and earlier rehabilitation.

Adult↗

What is a clubhouse? Report on the ICCD 1996 survey of USA clubhouses.

This article summarizes the findings from the ICCD 1996 Clubhouse Survey for the 173 respondent clubhouses located in the United States. It is our intent in the present article to identify commonalties in clubhouse organizational structure and practice across diverse geographic areas of the USA and within diverse health care systems, and, thereby, to identify typical or 'average' clubhouse performance in a variety of organizational and practice domains.

Activities of Daily Living↗

IgA-gliadin antibodies, IgA-containing circulating immune complexes, and IgA glomerular deposits in wasting marmoset syndrome.

BACKGROUND: Marmosets in captivity are highly susceptible to wasting marmoset syndrome (WMS), the aetiology of which is still not fully determined. METHODS: The level of IgA-gliadin antibodies (IgA-AGA), of IgA-containing circulating immune complexes (IgA-CIC), and the degree of glomerular IgA deposits were compared between marmosets suffering from WMS and animals not affected by the disorder. RESULTS: Both IgA-AGA and IgA-CIC were demonstrable in all groups of monkeys investigated. IgA-AGA and IgA-CIC were significantly higher in monkeys with WMS than in non-affected animals. There was a significant correlation between the glomerular IgA-deposition and titre of IgA-AGA. The group of marmosets strongly positive for glomerular IgA deposits comprised significantly more animals suffering from WMS than the group without deposits. In the diet of the animals a considerable amount of gliadin-like cereal proteins was assayed. CONCLUSIONS: There are several parallels between the human disorders (coeliac disease and IgA-nephropathy/Berger's disease) and the changes observed in WMS. It should be further investigated if WMS in marmosets is a suitable animal model for both human diseases.

Animals↗

IgM/IgA nephropathy in callitrichids: antigen studies.

Renal tissues of callitrichids with IgM nephropathy were immunohistochemically examined for the participation of IgA in pathogenesis. In 58 histopathologically nephropathy-positive kidneys, IgM predominated in 20 cases and IgA in 7 cases, and in 31 cases both immunoglobulins were rated to be approximately equally involved. The disease, therefore, might be described as IgM/IgA nephropathy. The renal tissues and sera were also tested for nutritional antigens or antinutritional antigen antibodies, using immunohistochemistry and Western blots (tissues) and enzyme-linked immunosorbent assay (sera). Evidences of nutritional antigens in the renal tissues were inconclusive, although circulating IgG class antibodies against cereals, milk, and egg proteins were present in quite a number of sera. Particular consideration was paid to IgA-antigliadin antibodies, which were statistically significantly associated with nephropathy as were IgA rheumatoid factors. The findings are discussed in relation to human IgA and IgM nephropathies.

Animals↗

Cooperative binding properties of restriction endonuclease EcoRII with DNA recognition sites.

EcoRII is a member of the expanding group of type IIe restriction endonucleases that share the distinguishing feature of requiring cooperativity between two recognition sites in their substrate DNA. To determine the stoichiometry of the active DNA-enzyme complex and the mode of cooperative interaction, we have investigated the dependence of EcoRII cleavage on the concentration of EcoRII dimers. Maximal restriction was observed at dimer/site ratios of 0.25 and 0. 5. The molecular weight of the DNA-enzyme complex eluted from a gel filtration column also corresponds to a dimeric enzyme structure bound to two substrate sites. We conclude that one EcoRII dimer is sufficient to interact cooperatively with two DNA recognition sites. A Lac repressor "barrier" bound between two normally reactive EcoRII sites did not inhibit restriction endonuclease activity, indicating that cooperativity between EcoRII sites is achieved by bending or looping of the intervening DNA stretch. Comparative cleavage of linear substrates with differently spaced interacting sites revealed an inverse correlation between cleavage rate and site distance. At the optimal distance of one helical turn, EcoRII cleavage is independent of the orientation of the recognition sequence in the DNA double strand.

Bacterial Proteins↗

Subtype-specific endothelin-A and endothelin-B receptor desensitization correlates with differential receptor phosphorylation.

In the rat cardiovascular system endothelin-1 (ET-1) elicits prolonged physiologic responses mediated by the ETA receptor, whereas the effects mediated by the ETB receptor are transient. The molecular mechanisms for the subtype-specific responses are not yet clear. However, post-translational modifications such as phosphorylation and palmitoylation may play an important role. In Sf9 cells overexpressing the human ETA and ETB receptors, both subtypes are palmitoylated. However, only the ETB but not the ETA receptor is phosphorylated in a ligand-dependent manner. Because phosphorylation is believed to play an important role in ligand-dependent receptor inactivation, we analyzed whether the differential phosphorylation of the ETA and ETB receptors reflects a differential mechanism of receptor inactivation. Using a modified inositol phosphate accumulation assay, we analyzed CHO cells that expressed the ETA or ETB receptor. The ETB receptor was deactivated almost completely within 5 min after agonist stimulation, whereas stimulation of the ETA receptor resulted in sustained activation, i.e., > 90% of the initial activity was maintained after 5 min of ligand stimulation and > 30% after 20 min. A strong correlation was observed between the time course of ETA receptor inactivation and ETA receptor internalization. The endogenous ETA receptor in Rat-1 cells produced a prolonged stimulation of phospholipase C similar to that seen in CHO cells. Therefore, the sustained signaling activity of the ETA receptor is not a property only of recombinant cell lines. Together, our data suggest rapid ETB receptor inactivation due to phosphorylation and delayed ETA receptor inactivation by internalization. These mechanisms adequately reflect the differential response patterns of the ET receptors under physiologic conditions.

Animals↗

So this is what it's like: struggling to survive in pediatric intensive care.

This is the story of my daughter's first 3 months of life, a time when we both struggled to survive while she was all but subsumed by scientific technology. Part I describes some common and dangerous failures of relationship which occur in busy hospitals. Part II describes the feelings of hope that arose in me not from any improvement in my child's condition, but from the ability of a few people to step outside of technology and science and risk what the others could not--authentic and caring engagement.

Anecdotes as Topic↗

Subtype-specific desensitization of human endothelin ETA and ETB receptors reflects differential receptor phosphorylation.

Endothelins regulate blood pressure in mammals through G protein-coupled receptors. Two receptor subtypes, ETA and ETB, exist which differ by their agonist profiles. Here we show subtype-specific differences in the inactivation of these endothelin receptors. Using a modified inositol phosphate accumulation assay, we found that stimulation of ETA by endothelin-1 results in sustained activation of the subtype, retaining >30% of its initial activity even 20 min after agonist administration, whereas the ETB rapidly deactivated after agonist stimulation, losing >80% of its initial activity within 5 min after endothelin application. The discrepancy in receptor inactivation is reflected by subtype-specific differences in receptor phosphorylation. Whereas ETA failed to undergo ligand-induced phosphorylation, the ETB was rapidly phosphorylated in response to agonist stimulation. By contrast, the kinetics of ligand-induced internalization were essentially identical for the receptor subtypes, suggesting endothelin receptor internalization being independent of ligand-induced receptor phosphorylation. Interestingly, a strong correlation was observed between the time course of ETA inactivation and ETA internalization. Therefore, our data suggest a subtype-specific inactivation of human endothelin receptors: fast receptor phosphorylation in the case of ETB and slow receptor internalization in the case of ETA. Subtype-specific modulation of endothelin receptors may account for the short-term hypotensive effects of endothelins via rapidly down-regulating ETB receptors and the long-lasting hypertensive effects due to sustained ETA activation.

Animals↗

Cloning and functional characterization of the ornithokinin receptor. Recognition of the major kinin receptor antagonist, HOE140, as a full agonist.

Kinins are proinflammatory peptides that dilate vessels, increase vascular permeability, contract smooth muscles, and provoke pain. The known mammalian kinin receptors are classified as two subtypes, i.e. the B1 receptor triggered by [des-Arg9]bradykinin and inhibited by [des-Arg9,Leu8]bradykinin, and the B2 receptor stimulated by bradykinin and antagonized by HOE140. Here we report the cloning of a non-mammalian kinin receptor gene amplified from genomic chicken DNA. The protein predicted from the open reading frame shows 31 and 49% sequence identity to the human B1 and B2 receptors, respectively, suggesting that it represents a G protein-coupled receptor of the kinin receptor family. The recombinantly expressed chicken receptor had IC50 values of 4.7 nM for the authentic ligand, ornithokinin ([Thr6,Leu8]bradykinin), 3.8 nM for HOE140, and >/=10 microM for bradykinin, [des-Arg9]bradykinin, and [des-Arg9,Leu8]bradykinin. Ornithokinin and HOE140 at nanomolar concentrations stimulated intracellular inositol phosphate accumulation and induced a significant transient rise in intracelluar free Ca2+, whereas bradykinin was ineffective even at 100 nM. Hence the principal B2 receptor antagonist HOE140 is a potent agonist of the chicken kinin receptor. This unique pharmacological profile classifies the ornithokinin receptor as a novel subtype among kinin receptors and will facilitate further molecular studies on ligand binding and receptor activation.

Adrenergic beta-Antagonists↗

Focus luminescence assay: macroscopically visualized foci of human cytomegalovirus and varicella zoster virus infection.

The plaques or foci of certain viruses due to their small size have to be counted microscopically, e.g., human cytomegalovirus (HCMV). The focus luminescence assay (FLA) described below generates macroscopic images as a result of the magnification due to scattered emitted light, and provides a hard copy using autoradiography or video imaging. Foci are detected according to an immunohistochemical protocol with horseradish peroxidase or alkaline phosphatase antibody conjugates which convert substrate into a luminescent product. Detection of varicella zoster virus (VZV) foci developed with a specific substrate-enhancer combination was so sensitive that 20-times lower primary antibody concentrations were effective than those required for conventional immunohistochemical staining. This method for HCMV and VZV may allow quantitative infectivity and focus reduction assays for viruses which produce little or no CPE.

Acyclovir↗

Relationship between human genotype and phenotype of N-acetyltransferase (NAT2) as estimated by discriminant analysis and multiple linear regression: 1. Genotype and N-acetylation in vivo.

Twenty-six healthy Caucasian subjects were evaluated for polymorphic N-acetyltransferase (NAT2) metabolic activity in vivo by sulfamethazine phenotyping and for their respective NAT2 genotype. Application of discriminant analysis allowed the separation of the rapid and slow acetylators solely on the base of their respective mutation pattern with identical results as achieved by the classical method of discrimination according to the phenotyping results. Multiple linear regression analysis was used to obtain a quantitative relationship between allelic pattern and the phenotypic outcome. It is shown that the computation methods produce relationships enabling the influence of particular mutations and/or allelic configurations on the metabolic activity in vivo to be estimated. This may be important in cases of discordant or overlapping phenotype and genotype results as well as in investigating the NAT2 polymorphism as a risk factor for cancer and other disease in epidemiological studies.

Acetylation↗

Different modes of inhibition by adamantane amine derivatives and natural polyamines of the functionally reconstituted influenza virus M2 proton channel protein.

The influenza virus M2 protein, target of the antiviral drugs amantadine and rimantadine, forms a proton channel which functions during virus uncoating and maturation by modifying the pH in virions as well as in trans-Golgi vesicles. We studied the influence of different ionic gradients on the inhibition of the proton translocation activity of isolated, baculovirus-expressed M2 protein reconstituted into liposomes. Two distinct patterns of inhibition were observed. A group of amphiphilic amines including amantadine, cyclooctylamine and rimantadine inhibited M2 effectively in the presence of physiological Na+ concentrations. The 10-fold greater activity of rimantadine over amantadine and the 100-fold stronger effect of cyclooctylamine compared to cyclopentylamine matched the relative activities in influenza virus-infected cells. A completely different inhibitory pattern emerged for the polyamines spermine, spermidine and putrescine. Polyamines have recently been identified as the 'intrinsic' rectifiers of a class of potassium channels and shown to interact with acidic amino acid residues lining and flanking the channel pore. In the presence of a physiological Na+/K+ gradient their minimal inhibitory concentrations for influenza virus M2 protein were 100, 400 and 500 microM, polyamine levels reported to exist in oocytes. In conditions depleted for Na+, polyamines inhibited M2 at concentrations two to three orders of magnitude lower. The data suggest that influenza virus M2 protein possesses a binding site for polyamines, distinct from the amantadine binding site, which is normally masked by Na+ and which could be targeted by selective antiviral inhibitors.

Adamantane↗

The early experience of a voluntary small group insurance program utilizing managed care plans.

HealthCare Group of Arizona (HCGA), a state-sponsored, voluntary health insurance purchasing program offering prepaid health plans to small businesses, became operational in 1988. This article summarizes the results from a wide-ranging evaluation of that program and discusses their implications. In general, enrollees were satisfied with their experience in their plans. HCGA did not appear to attract an adverse mix of health risks, and service utilization rates were consistent with HMO industry averages. However, these findings varied across health plans and the marketing approaches they adopted. Enrollment growth in HCGA has been steady, but premium subsidies may be necessary if HCGA is to substantially increase its enrollment of low-wage, uninsured workers.

Adolescent↗

Palmitoylation of endothelin receptor A. Differential modulation of signal transduction activity by post-translational modification.

Post-translational modifications such as phosphorylation and palmitoylation play important roles for the function and regulation of receptors coupled to heterotrimeric guanyl nucleotide-binding proteins. Here we demonstrate that the human endothelin receptor A (ETA) incorporates [3H]palmitate. Mutation of a cluster of five cysteine residues present in the cytoplasmic tail of ETA into serine or alanine residues completely prevented palmitoylation of the receptor. The ligand binding affinity of the non-palmitoylated ETA mutants was essentially unchanged as compared to the palmitoylated wild type ETA suggesting that the replacement of the cysteine residues did not alter the overall structure of the receptor. Furthermore, the ligand-induced stimulation of adenylyl cyclase by the mutant ETA was unaffected by the mutation. In contrast, the mutated non-palmitoylated receptors but not the wild type receptor failed to stimulate phosphatidylinositol hydrolysis by phospholipase C activation upon challenge by endothelin-1. Furthermore, the mutant receptors failed to stimulate the ligand-induced transient increase in the cytoplasmic calcium seen with the wild type ETA. Endothelin-1 induced mitogenic stimuli via the wild type receptors but not through the mutated receptors suggesting an important role for phospholipase C in this signal transduction pathway. The differential regulation of distinct signal transduction pathways by post-translational modification suggests that palmitoylation of the ETA provides a novel mechanism of modulating ETA receptor activity.

Amino Acid Sequence↗

Income, health status, and insurance coverage of small group employees in a voluntary purchasing arrangement.

The ongoing health care reform discussion has highlighted the problems of insuring small group employees. Several state and private initiatives have attempted to address some of these problems through the formation of voluntary small group purchasing arrangements. This article uses data from one such initiative, Health Care Group of Arizona (HCGA), to describe the income, health status, and prior insurance of small group employees who enrolled in prepaid health plans through HCGA. It also compares employee enrollees to nonenrollees along these dimensions. The findings suggest that HCGA enrollees had relatively low incomes and that about three-quarters were without health insurance prior to enrollment. Higher income employee enrollees were more likely to report health conditions at enrollment even after controlling for other factors including age. Enrollees were less likely than nonenrollees to have prior health insurance but were more likely to be drawn from lower income groups and to report recent health conditions.

Adolescent↗

Type III restriction endonucleases translocate DNA in a reaction driven by recognition site-specific ATP hydrolysis.

Type III restriction/modification systems recognize short non-palindromic sequences, only one strand of which can be methylated. Replication of type III-modified DNA produces completely unmethylated recognition sites which, according to classical mechanisms of restriction, should be signals for restriction. We have shown previously that suicidal restriction by the type III enzyme EcoP15I is prevented if all the unmodified sites are in the same orientation: restriction by EcoP15I requires a pair of unmethylated, inversely oriented recognition sites. We have now addressed the molecular mechanism of site orientation-specific DNA restriction. EcoP15I is demonstrated to possess an intrinsic ATPase activity, the potential driving force of DNA translocation. The ATPase activity is uniquely recognition site-specific, but EcoP15I-modified sites also support the reaction. EcoP15I DNA restriction patterns are shown to be predetermined by the enzyme-to-site ratio, in that site-saturating enzyme levels elicit cleavage exclusively between the closest pair of head-to-head oriented sites. DNA restriction is blocked by Lac repressor bound in the intervening sequence between the two EcoP15I sites. These results rule out DNA looping and strongly suggest that cleavage is triggered by the close proximity of two convergently tracking EcoP15I-DNA complexes.

Adenosine Triphosphatases↗

Restriction endonucleases functionally interacting with two DNA sites.

Simultaneous interaction with two recognition sites was found to be a precondition for DNA cleavage by certain type-II and type-III restriction endonucleases. Nevertheless, the molecular mechanisms of the protein-DNA interaction are different between members of both classes of enzymes.

Binding Sites↗