PubMed Health⌕ Search

Biomedical subjects

S Seiler

Publications and source records attributed to S Seiler.

At least 19 recordsLinked to original sources
PubMed2006

On the weight-bearing function of the medial coronoid process in dogs.

The shape of and proportions between the surface areas of the medial coronoid process (MCP) and the fovea of the radial head were determined in 88 juvenile dogs and 146 adult dogs grouped as giant, large, mid-sized, chondrodystrophic, or small dogs. Thereby, the longitudinal (length) and transverse (width) extension of the MCP and fovea of the radial head have been measured. Original values were used to describe changes of the parameters attributed to growth. Normalized values (i.e. values expected in case of a width of the fovea of the radial head of 20 mm) were used to determine potential differences between constitutional types. All original values increased during growth (P < 0.05) except for the width and length of the MCP in chondrodystrophic and small breeds. Normalized values revealed a proportional decrease in width and length of the MCP during growth (P < 0.05) compared with the radial head. In adults, the normalized MCP was widest in giant dogs followed by large, mid-sized, small, and chondrodystrophic breeds. The MCP was also longest in giant dogs but shortest in large and chondrodystrophic dogs with those of large dogs being significantly (P < 0.05) shorter than those in giant, mid-sized and small dogs. Present results suggest that a deficiency in length-growth of the MCP--which has been present especially in large dogs--results in smaller humeral contact areas and decreased weight-bearing capacity of the MCP. Because loading forces acting on the MCP increase with body weight, the condition noted in large dogs might increase the risk of fragmentation of the MCP in these.

Aging↗
PubMed2006

Advances in in vitro and in vivo models for studying the staphylococcal factors involved in implant infections.

Implant infections due to staphylococci are one of the greatest threats facing patients receiving implant devices. For many years researchers have sought to understand the mechanisms involved in the adherence of the bacterium to the implanted device and the formation of the unique structure, the biofilm, which protects the indwelling bacteria from the host defence and renders them resistant to antibiotic treatment. A major goal has been to develop in vitro and in vivo models that adequately reflect the real-life situation. From the simple microtiter plate assay and scanning electron microscopy, tools for studying adherence and biofilm formation have since evolved to include specialised equipment for studying adherence, flow cell systems, real-time analysis of biofilm formation using reporter gene assays both in vitro and in vivo, and a wide variety of animal models. In this article, we discuss advances in the last few years in selected in vitro and in vivo models as well as future developments in the study of adherence and biofilm formation by the staphylococci.

Animals↗
PubMed2005

Postnatal modelling of the humeroantebrachial contact areas of radius and ulna in dogs.

Necropsy dogs (n = 234) ranging in age between 2 days and 17 years were examined to characterize the cross-sectional shape of the humeroantebrachial contact area of the radius and ulna on radioulnar scans of giant, large, mid-sized, small, and chondrodystrophic breeds. During growth, the contact areas became more circular in shape in all breeds, those in small dogs remained most elliptic. Smallest normalized heights (distance between the tip of the anconeal process and the most proximal aspect of the cranial margin of the radial head = RUH, distance between the tip of the anconeal process and the cranial tip of the medial coronoid process = UH) and depths (distance determined in a right angle to RUH = RUD, distance determined in a right angle to UH = UD) were noted in large and giant breeds with no significant difference between these. In juveniles, a decrease in UD was correlated with a decrease in UH in all breeds as was a decrease in RUD correlated with a decrease in RUH, whereas in non-arthrotic adults this condition could only be proven for mid-sized dogs and small breeds but not for giant, large and chondrodystrophic dogs. The average radioulnar and ulnar heights and depths (as seen in non-arthrotic adults) were calculated to be obtained in mid-sized dogs at least 3-4 weeks earlier than in large dogs. Lipping of the cranial margin of the radial head was significantly (P < 0.001) associated with lesion(s) of the articular surface (i.e. erosion of the articular cartilage and subchondral bone and/or fragmentation of the medial coronoid process) and caused additional change in shape of this contact area, which was then even more circular. However, the variables evaluated (RUH, RUD, UH, UD) allowed only poor discrimination between constitution types and between non-arthrotic and arthrotic joints.

Aging↗
PubMed2004

Variation in the ossification process of the anconeal and medial coronoid processes of the canine ulna.

This morphological and radiographic study investigates the ossification process of the anconeal and medial coronoid processes of the ulna in a sample of 142 dogs ranging in age from neonatal to 44 weeks. The anconeal process was noted to develop by appositional ossification, formation of a separate ossification center, or a combination of both. Several developmental stages of the ossification center of the anconeal process as well as its anatomic position and radiographic appearance are described. Differences have been noted in the shape of this ossification center as well as the ossification process itself. The medial coronoid process develops exclusively by appositional ossification. Unlike ossification of the anconeal process, ossification of the medial coronoid process was completed earlier (p < 0.05) in smaller than in the larger dogs. In smaller dogs, both the medial coronoid and anconeal processes were found to be mature by the age of 16 weeks. In the larger dogs, ossification of the anconeal process was completed not before 14 weeks of age and ossification of the medial coronoid process was completed about 6 weeks later.

Animals↗
PubMed2000

Cargo binding and regulatory sites in the tail of fungal conventional kinesin.

Here, using a quantitative in vivo assay, we map three regions in the carboxy terminus of conventional kinesin that are involved in cargo association, folding and regulation, respectively. Using C-terminal and internal deletions, point mutations, localization studies, and an engineered 'minimal' kinesin, we identify five heptads of a coiled-coil domain in the kinesin tail that are necessary and sufficient for cargo association. Mutational analysis and in vitro ATPase assays highlight a conserved motif in the globular tail that is involved in regulation of the motor domain; a region preceding this motif participates in folding. Although these sites are spatially and functionally distinct, they probably cooperate during activation of the motor for cargo transport.

Adenosine Triphosphatases↗
PubMed1999

Functional anatomy of the kinesin molecule in vivo.

We have developed an assay that allows the functional efficiency of mutant kinesins to be probed in vivo. We show here that the growth rate of the filamentous fungus Neurospora crassa can be used as a sensitive reporter for the ability of mutant kinesins to suppress the phenotype of the kinesin null mutant of Neurospora. Truncation mutants, internal deletion mutants and chimeras, in which homologous domains were exchanged between different fungal kinesins, were generated and transformed into the kinesin-deficient strain. None of the mutations affect motor velocity in vitro, but even minor alterations in the tail domain severely compromise kinesin's performance in vivo. The analysis of these mutants has identified subdomains in the stalk and tail likely to be involved in cargo binding and/or regulation of motor activity. The phenotypes of several mutants strongly suggest that kinesin requires a folded conformation to achieve full functionality in vivo. Folding critically depends on two flexible domains in the stalk that allow an interaction of the tail with the neck/hinge region near the catalytic motor domain. The assay has proven to be a valuable tool in the analysis of kinesin function in vivo and should help to characterize the sites involved in intra- and intermolecular interactions.

Amino Acid Sequence↗
PubMed1999

Iron management: innovative solutions to persistent challenges--focus on Ferrlecit.

The use of sodium ferric gluconate in sucrose injection (Ferrlecit) in the treatment of anemia in patients with end stage renal disease (ESRD) was the major topic at the symposium "Iron Management: Innovative Solutions to Persistent Challenges," held April 14, 1999 during the annual ANNA 30th National Symposium in Baltimore, Maryland. Chairperson Susan Vogel, MHA, RN, CNN, addressed the challenges of anemia management and the limitations of oral iron supplements. She described available intravenous (i.v.) iron therapies and reviewed clinical trial data that demonstrated an excellent safety and efficacy profile for the newly approved i.v. iron supplement, sodium ferric gluconate. Suzanne Schweitzer, RPh, MPH, discussed iron metabolism and the U.S. labeling for sodium ferric gluconate, with a focus on dosing and administration. In the final presentation, Suzanne Seiler, RN, described her clinic's experience with sodium ferric gluconate and provided an experimental dosing and monitoring protocol. Together, these presentations suggest that sodium ferric gluconate is an important new tool for meeting the challenges of iron management in ESRD patients.

Anemia, Iron-Deficiency↗
PubMed1998

Conditional lineage ablation to model human diseases.

Cell loss contributes to the pathogenesis of many inherited and acquired human diseases. We have developed a system to conditionally ablate cells of any lineage and developmental stage in the mouse by regulated expression of the diphtheria toxin A (DTA) gene by using tetracycline-responsive promoters. As an example of this approach, we targeted expression of DTA to the hearts of adult mice to model structural abnormalities commonly observed in human cardiomyopathies. Induction of DTA expression resulted in cell loss, fibrosis, and chamber dilatation. As in many human cardiomyopathies, transgenic mice developed spontaneous arrhythmias in vivo, and programmed electrical stimulation of isolated-perfused transgenic hearts demonstrated a strikingly high incidence of spontaneous and inducible ventricular tachycardia. Affected mice showed marked perturbations of cardiac gap junction channel expression and localization, including a subset with disorganized epicardial activation patterns as revealed by optical action potential mapping. These studies provide important insights into mechanisms of arrhythmogenesis and suggest that conditional lineage ablation may have wide applicability for studies of disease pathogenesis.

Action Potentials↗
PubMed1998

Tuberculosis infection and anergy in hemodialysis patients.

Patients on hemodialysis are at increased risk for developing active tuberculosis (TB) after primary infection. Although this increased risk is well documented, the prevalence of TB infection, as indicated by a positive tuberculin skin test (TST), is not well described. End-stage renal disease is also known to be a risk factor for skin test anergy, but the rate of anergy in hemodialysis patients is unclear. We sought to identify rates of anergy and TST positivity in patients at four hemodialysis units in St Louis, Missouri, from June 1996 through August 1996. Data obtained from patients and medical records included age, years on hemodialysis, medical history, and basic laboratory data. Patients without a history of TB or a positive TST had a TST with Tubersol, as well as candida and tetanus controls, placed by the Mantoux method. Tests were read 48 hours later. Of the patients enrolled at these units, 307 of 331 (93%) were evaluated. Patients had a mean age of 58 years (range, 19 to 91 years) and had been on hemodialysis for a mean of 3.7 years (range, 1 week to 18.7 years). Blacks made up 81% of the population. A history of a positive TST was obtained from 24 patients (8%), and an additional seven (2%) had a history of active TB. Of the 276 patients tested, 93 did not respond to either control antigen, but five of these patients had a positive TST, leaving 88 (32%) anergic. Anergy was related to age, immunosuppressive drug use, and the reagents used, but not to urea reduction ratio. Positive TSTs were found in 17 of 188 of nonanergic patients (9%) (6% of all tested patients). Overall, 48 of 307 patients (16%) had a positive TST or history of TB. TB or a positive TST was associated with liver disease and peptic ulcer disease, but not socioeconomic status. All 17 newly identified TST-positive patients received chest radiographs. No new cases of active TB were found. Only two of 17 of these patients (12%) were started on isoniazid (INH) prophylaxis. We identified high rates of TST positivity and anergy in the hemodialysis patients tested. Hemodialysis patients should receive regular TST screening, and INH prophylaxis needs to be more strongly encouraged. Studies are ongoing to define the rate of TST conversion over time.

Adult↗
PubMed1997

Kinesin is essential for cell morphogenesis and polarized secretion in Neurospora crassa.

Kinesin is a force-generating molecule that is thought to translocate organelles along microtubules, but its precise cellular function is still unclear. To determine the role of kinesin in vivo, we have generated a kinesin-deficient strain in the simple cell system Neurospora crassa. Null cells exhibit severe alterations in cell morphogenesis, notably hyphal extension, morphology and branching. Surprisingly, the movement of organelles visualized by video microscopy is hardly affected, but apical hyphae fail to establish a Spitzenkörper, an assemblage of secretory vesicles intimately linked to cell elongation and morphogenesis in Neurospora and other filamentous fungi. As cell morphogenesis depends on polarized secretion, our findings demonstrate that a step in the secretory pathway leading to cell shape determination and cell elongation cannot tolerate a loss of kinesin function. The defect is suggested to affect the transport of small, secretory vesicles to the site involved in protrusive activity, resulting in the uncoordinated insertion of new cell wall material over much of the cell surface. These observations have implications for the presumptive function of kinesin in more complex cell systems.

Biological Transport↗
PubMed1997

Varied approaches to tuberculosis control in a multihospital system.

OBJECTIVES: To document the actual tuberculosis (TB) control policies and procedures in a nonoutbreak setting in a variety of hospitals. To determine if any particular practices are linked to higher rates of employee tuberculin skin-test conversion. DESIGN: Survey of hospital occupational health and infection control practitioners for the year 1994 regarding hospital TB policies. Review of hospital records to verify the number of patients with TB at each hospital and to verify the number of employees with positive tuberculin skin tests. Smoke-stick testing of negative-pressure ventilation rooms. SETTING: A 13-hospital health system in the Midwest. RESULTS: Hospitals ranged in size from 40 to 1,208 beds (median 220) and employed 150 to 6,500 workers (median 875). There were seven rural and six urban centers, including four teaching hospitals. All 13 hospitals had TB control plans, and all performed annual tuberculin skin testing on employees. Annual skin-test positivity rates ranged from 0% to 1.0% (median 0.3%). Negative-pressure ventilation rooms were available in 11 hospitals. The percentage of negative-pressure rooms with effective negative pressure ranged from 44% to 100% (median 95%). Three of the 13 hospitals used high-efficiency particulate air (HEPA) masks as primary personal respiratory protection, and 8 used dust-mist or dust-mist-fume masks. We found no relation between the type of face mask used, number of functional negative-pressure rooms, or hospital TB risk category, and employee skin-test conversion rates. CONCLUSIONS: Considerable variation existed in the TB control policies and procedures between hospitals, but employee TB skin-test conversion rates were low in all settings.

Cross Infection↗
PubMed1996

The effects of nitric oxide (NO) on platelet membrane receptor expression during activation with human alpha-thrombin.

Nitric oxide (NO) is known as a regulator of platelet function by its anti-adhesive, anti-aggregating, and disaggregating properties. We investigated the modulating effects of the NO-releasing compound SIN-1 (3-morpholino-sydnonimine) on platelet surface glycoprotein (GP) expression during stimulation with human alpha-thrombin. Analysis was performed with two-color flow cytometry using fluoresceine-isothiocyanate (FITC) and phycoerythrin-(PE)-conjugated monoclonal antibodies (MoAbs) directed against GPIb CD42b), GP IIb-IIIa (CD41), P-selectin (CD62P), and MoAb PAC-1 directed against activated GP IIb-IIIa. Preincubation of platelets with SIN-1 (IC50: 1 microM) significantly decreased expression of both total and activated GP IIb-IIIa, and P-selectin in platelets stimulated with thrombin (ED50: 0.05 U/ml), whereas thrombin-induced downregulation of GP Ib was not attenuated. P-selectin expression increased in thrombin-stimulated platelets over time; in contrast, activated GP-IIb-IIIa decreased after an initial peak, indicating that thrombin-induced GP IIb-IIIa activation is spontaneously reversible. SIN-1 reduced P-selectin expression only when added before or at the same time as thrombin, whereas conformationally changed GP-IIb-IIIa was significantly reversed at up to 60 minutes after stimulation by SIN-1. In conclusion, NO attenuates activation marker expression in a dose and time dependent manner. GP-IIb-IIIa is highly sensitive to NO which not only prevents receptor activation but also promotes reversal of activated GP IIb-IIIa complex.

Blood Platelets↗
PubMed1995

[Transgenicular amputation with special reference to partial secondary femoral condyle resection].

During the last five years 54 patients (mean age 69 years) have undergone a unilateral, transgenicular (through-knee) amputation, instead of an impending amputation through the thigh. The indication for surgery was a chronic, or an acute critical ischemia of the leg. In 32 and 22 cases respectively, amputations have been preceded by a multitude of reconstructive measures. Uncomplicated stump healing was observed in 25 of 51 survivors (49%). Disturbances in the wound healing process necessitated further amputation in 26 cases (51%). In 13 of these cases the advantage of the transgenicular amputation could be retained by a partial femoral condylectomy, whereas in the other 13 cases a thigh amputation was inavoidable. Thus, in three out of four of the survivors, a long, strong stump with a good terminal load-carrying capacity could be retained which, when supplied by a prosthesis, led to the recovery of the original walking ability in 90% of these cases.

Aged↗
PubMed1993

Psychosocial aspects of Parkinson's disease.

Although Parkinson's disease has a definite neurologic basis, patients and relatives experience a multitude of stresses, only partly related to motor symptoms. Subjective and behavioral problems may be regarded as secondary disease symptoms. In an integrated approach, patients and relatives receive psychological counseling and learn new coping strategies for everyday situations. Results show that even elderly patients can make use of structured psychological interventions and change dysfunctional behaviors and cognitions. Measures specifically adjusted to Parkinson's disease are aimed at helping patients make better use of the beneficial effects of medication and counteract the possible negative effects of social and emotional stressors. Relatives need information about the disease and training to cope adequately with difficult caring situations. Future evaluation of medical treatment of Parkinson's disease should consider the interaction of psychological factors and symptom intensity. This interaction may result in momentary changes in the effects of medication because of psychological conditions. In the early stages of the disease, medication has the most positive effect, and psychological interventions should also have the most benefit.

Aged↗
PubMed1991

Imidazoquinoline derivatives: potent inhibitors of platelet cAMP phosphodiesterase which elevate cAMP levels and activate protein kinase in platelets.

Compounds containing the imidazoquinoline nucleus are a new class of potent, broad-spectrum inhibitors of platelet aggregation. This report describes studies with a simply-substituted imidazoquinoline (BMY 20844) and several new ether-linked side chain derivatives (BMY 21638 and BMY 43351). These compounds are potent inhibitors of platelet cAMP phosphodiesterase (IC50 values: BMY 20844, 1.3 X 10(-8); BMY 21638, 2 X 10(-10); and BMY 43351, 1 X 10(-10) M, measured using 0.15 microM cAMP) but have little effect on platelet homogenate cGMP phosphodiesterase (IC50 greater than 10(-5) M). Inhibition of different cAMP phosphodiesterase isozymes was tested to determine if the compounds inhibited similar isozymes in other tissues. Rabbit heart cAMP phosphodiesterase isozymes were resolved by ion-exchange chromatography and three peaks of activity were obtained. BMY 20844 inhibited only fraction III (a "cGMP-inhibitable, low Km" cAMP-specific phosphodiesterase) with an IC50 value of 5 X 10(-8) M. These compounds also inhibited canine cardiac sarcoplasmic reticulum membrane-bound "cGMP-inhibitable, low Km" cAMP-specific phosphodiesterase with virtually the same potency as inhibition of cAMP phosphodiesterase in platelet homogenate. In washed platelets these compounds elevated cAMP levels and activated the platelet cAMP dependent protein kinase. Activation of cAMP-dependent protein kinase was determined by cAMP-dependent protein kinase ratio measurements and phosphorylation of intracellular proteins. These studies suggest that this potent new class of agents inhibits platelet phosphodiesterase activity in intact platelets causing an elevation in cAMP levels sufficient to activate the cAMP-dependent protein kinase and stimulate protein phosphorylation. This mechanism is, at least in part, responsible for the ability of these compounds to prevent platelet aggregation and thrombosis in experimental animal models.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1990

SQ-27986 inhibition of platelet aggregation is mediated through activation of platelet prostaglandin D2 receptors.

SQ-27986, a oxabicycloheptane derivative, potently inhibits ADP-, collagen- and arachidonic acid-induced platelet aggregation in human platelet-rich plasma. Human platelet aggregation induced by ADP is inhibited by SQ-27986 (EC50 = 22nM), and the inhibitory action of SQ-27986 can be prevented with N-0164, a PGD2 antagonist. By comparison, ADP-induced rat platelet aggregation is unaffected by SQ-27986 (IC50 greater than 80 microM). Washed human platelets treated with SQ-27986 exhibit elevated cAMP levels and activated cAMP-dependent protein kinase. Elevation of platelet cAMP levels (greater than 4 fold basal) and activation of the cAMP-dependent protein kinase (greater than 4 fold) are observed with SQ-27986 concentrations above 100 nM. The SQ-27986-induced elevation of cAMP can be prevented by N-0164. Lysed platelets treated with SQ-27986 showed stimulated adenylate cyclase activity. SQ-27986 competes with [3H]prostaglandin D2 binding to isolated platelet membranes (EC50 for SQ-27986 is 20 nM, which was more potent than cold PGD2 itself). Radiolabeled Iloprost binding is virtually unaffected by SQ-27986 (EC50 greater than 100 microM), indicating that SQ-27986 does not interact with platelet prostacyclin receptors. These studies indicate that SQ-27986 inhibits platelet aggregation by activating platelet adenylate cyclase via stimulation of platelet PGD2 receptors.

Adenosine Diphosphate↗
PubMed1990

Octimibate inhibition of platelet aggregation: stimulation of adenylate cyclase through prostacyclin receptor activation.

Octimibate inhibited ADP- and collagen-induced platelet aggregation in human, rabbit and rat platelet-rich plasma. Washed human platelets treated with octimibate had elevated cyclic AMP (cAMP) levels and cAMP-dependent protein kinase activity. When whole platelets were incubated with radiolabeled phosphate, octimibate produced an increase in the phosphorylation of platelet proteins with relative molecular weights of 22, 26, 50 and 80 kilodaltons. This pattern of protein phosphorylation is identical to that observed when the platelets were treated with forskolin, phosphodiesterase inhibitors or other compounds that elevate platelet cAMP levels. Octimibate also inhibited the rise in intracellular Ca++ caused by thrombin, as measured using Fura-2-loaded platelets, which is consistent with octimibate's ability to elevate platelet cAMP levels. When isolated platelet plasma membranes were treated with octimibate, adenylate cyclase activity was stimulated, reaching maximal activation at 1 microM octimibate. (The maximal activation of adenylate cyclase observed with octimibate is 70-75% of that observed with 10 microM PGE1.) This stimulation of platelet adenylate cyclase activity was enhanced by GTP. Octimibate competed for radiolabeled prostaglandin E1 and lloprost binding to isolated platelet membranes at submicromolar concentrations, but did not compete with radiolabeled prostaglandin D2 binding. These studies suggest that octimibate inhibits platelet aggregation by activating platelet adenylate cyclase through stimulation of platelet prostacyclin receptors.

Adenylyl Cyclases↗