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Biomedical subjects

M Wagner

Publications and source records attributed to M Wagner.

At least 415 records · Page 23Linked to original sources
PubMed1996

Oligomerization supports transport of a mutant secretory protein out of the endoplasmic reticulum.

To examine the transport of the single subunits of the glycoprotein complex gp80 (clusterin, apolipoprotein J), a marker protein for apical exocytosis and main secretory product of Madin-Darby canine kidney (MDCK) cells, several mutant cDNAs were constructed and expressed in the fibroblastic baby hamster kidney (BHK-21) cell line. In the absence of the second subunit the mutant proteins formed disulfide-linked homodimeric complexes. In the homodimeric form lys-gp45, a lysozyme-tagged mutant representing the C-terminal subunit, acquired competence for transport to the cell surface. Biogenesis and transport of this hybrid protein were also examined in stably transfected MDCK cells. In these cells which express both the endogenous gene and the mutant cDNA lys-gp45 was linked via disulfide bonds to the gp80 complex. These heterooligomeric complexes were secreted predominantly at the apical cell surface. Thus, oligomerization regardless of whether it resulted in homodimeric or heterooligomeric complexes conveyed transport competence to the mutant protein.

Animals↗
PubMed1995

NMDA/R1-antisense oligonucleotide influences the early stage of long-term potentiation in the CA1-region of rat hippocampus.

We have studied the role of the N-methyl-D-aspartate (NMDA)/R1 receptor subunit in the mechanism of long-term potentiation (LTP) using an antisense-oligodeoxynucleotide strategy. Antisense-oligodeoxynucleotide (aDON; 10 nmol) or sense-oligodeoxynucleotide (sDON) were applied into the right ventricle of 7 week old male Wistar rats every 12 h for 3 days. Thereafter, in hippocampal slices extracellular field potential recordings were made from the CA1 region. LTP was induced by tetanization of the Schaffer collaterals. In slices of rats pretreated with aDON the initial potentiation of the population spike (POP-spike) was significantly smaller than in those from saline controls and naive animals. The impairment of potentiation lasted for about 50 min posttetanus. However, the potentiation of the field excitatory postsynaptic potentials (fEPSPs) was significantly influenced for 15 min. In slices of rats pretreated with sDON only a small, insignificant difference in POP-spike and fEPSP potentiation was seen compared to saline controls. In the group pretreated with aDON the specific binding of [3H]glutamate to the NMDA-receptor subtype of hippocampal membranes was reduced to about 63% in comparison with the group treated with sDON. These results indicate that DONs reached the target region when applied intraventricularly and were able to suppress the translation of mRNA of the NMDA/R1 receptor subunit. They further support the assumption of the essential role of the NMDA/R1 receptor subunit in the induction of LTP.

Animals↗
PubMed1995

Analysis of second-site mutations that suppress the multiple drug resistance phenotype of the yeast PDR1-7 allele.

The yeast PDR1 locus encodes a member of the C6 zinc cluster family of transcriptional regulatory proteins. Among the targets of PDR1 is the yeast PDR5 locus. The product of this gene is a member of the ATP-binding cassette (ABC) transmembrane protein family and plays a major role in inhibitor efflux. Mutations in PDR1 affect the relative level of PDR5 transcript and can therefore result in increased or decreased drug resistance. We isolated three second-site suppressors of a PDR1-7 semidominant hyper-resistant mutation. These mutants were drug hypersensitive, as compared with isogenic controls. Two of the three mutations contained alterations in a putative DNA-binding domain. Significantly, the mutant proteins exhibited reduced DNA-binding capacity.

ATP-Binding Cassette Transporters↗
PubMed1995

Promoting inpatient directives about life-sustaining treatments in a community hospital. Results of a 3-year time-series intervention trial.

BACKGROUND: Hospitalization presents an opportunity for physicians to discuss advance directives with patients and to encourage completion of health care proxies. OBJECTIVE: To prospectively promote discussion and documentation of treatment-specific directives about life-sustaining interventions (cardiopulmonary resuscitation, admission to critical care units, mechanical ventilation, electrical cardioversion, and vasopressor therapy) among unselected medical inpatients in a community teaching hospital. METHODS: We conducted a time-series intervention trial from January 1, 1991, through June 30 1993, divided into three phases. During the education phase, we provided reminders, education, and feedback to attending physicians; during the intervention phase, we promoted a new documentation form for directives to be used by attending physicians; during the control phase, no interventions occurred. We studied consecutive patients (N = 1780) admitted to the hospital acute medical service in each of the following 10 periods: three in the education phase (n = 598), three in the intervention phase (n = 826), and four in the control phase (n = 356). The primary outcome measures were the frequency and content of directives documented by attending physicians in their patients' hospital charts. Secondary outcome measures included physicians' and patients' attitudes about directives, surveyed repeatedly. RESULTS: The proportion of inpatients with directives increased significantly during the intervention phase (62.5% vs 23.6% during the education phase and 25.3% during the control period, P < .001, Pearson chi 2 test). During the final intervention phase, 227 (83.2%) of 273 inpatients had directives documented in the hospital chart. Increases in clinically important ("impact") directives usually involved intensive care, not do-not-resuscitate status. Overall, 366 (86.7%) of 422 physician-attested directives agreed with the treatment preferences of interviewed patients (kappa ranges, 0.53 to 0.79). Physicians' attitudes about and interest in directives improved. CONCLUSIONS: Institutional interventions can facilitate attending physicians' documentation of treatment-specific directives about life-sustaining care for most medical inpatients. More research is needed to confirm the effect of these efforts on quality and cost of hospital care, patients' autonomy, and their eventual execution of durable directives and proxies.

Advance Care Planning↗
PubMed1995

Promoting completion of health care proxies following hospitalization. A randomized controlled trial in a community hospital.

BACKGROUND: The wider use of written advance directives is popular but problematic. We have shown previously that acute hospitalization in the era of the Patient Self-Determination Act can facilitate directive discussions and documentation. We investigated whether a simple educational intervention following hospitalization would increase patients' execution of durable health care proxies. METHODS: We studied a consecutive series of patients (n = 162) recently discharged from the acute care medical service of a community hospital where they had been interviewed about advance directives. The intervention group was randomized to receive an educational brochure and encouragement to execute durable health care proxies. The primary outcome was the proportion of patients in each group with completed durable health care proxies on file in their primary physicians' offices. RESULTS: Overall, only 20 (12.3%) of 162 patients had documented proxies, 17 of whom (85%) were 65 years of age or older, with no difference between the intervention and control groups (11 [13.3%] of 83 vs nine [11.4%] of 79, respectively). Subgroup analysis of elderly patients also revealed no intervention effect. Univariate analysis revealed three significant predictors of patients' proxy completion: patient age, whether patients had discussed directives in hospital with their physicians, and whether patients' physicians completed proxies for themselves. Multiple logistic regression analysis showed that these three variables interact to predict the probability of patients' executing proxies. CONCLUSIONS: Simple educational interventions, like those mandated by the Patient Self-Determination Act, are unlikely to increase patients' completion of durable healthcare proxies. Multidimensional interventions that target both elderly patients and their personal physicians should be tested in the future. Discussion in hospital about advance directives can be a useful component of such efforts.

Adolescent↗
PubMed1995

A global witch-hunt.

Explore the source record for details and available documents.

Attitude of Health Personnel↗
PubMed1995

Information processing during eye tracking as revealed by event-related potentials in schizophrenics, alcoholics, and healthy controls.

To further explore the hypothesis that schizophrenics are more distractable and/or have reduced processing resources available, event-related potentials (ERPs) and smooth pursuit eye movements (SPEM) were investigated in 20 medicated schizophrenics, 19 detoxified chronic alcoholics, and in a control group of 20 healthy subjects. Groups were matched for age and education. Eye tracking tasks and auditory oddball tasks were performed separately as well as simultaneously. In addition, an eye tracking condition with a task-irrelevant tone sequence was used to assess the effect of distraction. Schizophrenics showed a trend for poorer SPEM performance; alcoholics had no dysfunction in this task. Tracking accuracy did not change in either group when additional auditory stimuli were presented. P300 latency was delayed in both schizophrenics and alcoholics. P300 amplitude showed no overall group difference but it increased during the dual task in normals whereas it remained constant in patients. N100 amplitude was generally larger during the more complex conditions indicating heightened unspecific arousal. It is suggested that normals use increased arousal to mobilize additional resources and to allocate them to stimulus evaluation but schizophrenics and alcoholics are unable to do so. Results are more conform to a limited resources concept than to a filter deficit model of cognitive disturbances in schizophrenia and alcoholism.

Adolescent↗
PubMed1995

Presacral tumors: case report, review of the literature.

A case report involving a 42-year-old female is presented. The symptoms and objective physical findings manifest a diagnostic problem. The anatomical site of the tumor depends on the consideration of the numerous possible etiological factors, and one of which is the embryologic knowledge of the region involved. The clinical, pathological, and embryologic features of a case of presacral tumor is presented.

Adult↗
PubMed1995

Laser-assisted removal of a foreign body in the bronchial system of an infant.

BACKGROUND AND OBJECTIVE: Foreign body aspiration is an important cause of acute respiratory distress in children. Removal by use of rigid tracheobronchoscopy under general anesthesia is usually the treatment of choice, but this technique is sometimes unsuccessful. Thoracotomy in these instances often cannot be avoided. STUDY DESIGN/PATIENTS AND METHODS: Case report with review of the literature. The patient was 19 months old with an aspirated foreign body. A Neodym:YAG laser with a special small-size delivery system was inserted into the rigid "baby" bronchoscope. The Neodymium:YAG laser with a wave-length of 1,064 nm and a Helium-Neon 630 nm light guide provided an aiming beam to weaken and cut the aspirated chicken bone. RESULTS: The foreign body could be easily removed with a regular biopsy forceps. CONCLUSION: We discuss a patient in whom laser-assisted rigid tracheobronchoscopy obviated the need for thoracotomy.

Aluminum Silicates↗