PubMed HealthSearch

Biomedical subjects

K Fischer

Publications and source records attributed to K Fischer.

At least 19 recordsLinked to original sources

Multicenter dose-finding trial for thrombolysis with urokinase preactivated pro-urokinase (TCL 598) in acute myocardial infarction. German Preactivated Pro-Urokinase Study Group.

In a multicenter dose-finding study, the thrombolytic potency of urokinase preactivated pro-urokinase was evaluated. Sixty-two patients were randomly assigned to receive 250,000 U of urokinase plus either 4.5 mega U (group I: n = 33) or 6.5 mega U (group II: n = 29) of pro-urokinase. Patency rates were 36.4% (20.4-54.9%) vs. 54.5% (36.3-71.9%) (n = 27) at 60 minutes and 55.6% (32.5-70.6%) vs. 62.1% (42.3-79.3%) at 90 min into thrombolysis (n.s.). In a third group of 12 patients treated with 500,000 U of urokinase plus 6.5 mega U of pro-urokinase patency was achieved in 33.3% (9.9-65.1%) and 41.7% (15.2-72.3%) at 60 and 90 min, respectively. Patency rates at 24 hr follow-up angiography (n = 35) were 78.6% (49.2-95.3%), 85.7% (57.2-98.2%), and 85.7% (42.1-99.6%). Coagulation analysis in 37 patients revealed similar alterations in the three treatment groups with minor decreases in fibrinogen levels, moderate drops in plasminogen and alpha-2-antiplasmin levels, and moderate increases in the concentrations of the total fibrinogen/fibrin degradation products, the differences between the groups not being significant. Bleeding complications were observed in 12.9%, 13.8%, and 25% of patients in groups I, II, and III, respectively, mainly related to catheter sites. Hence, the safety profile of urokinase preactivated pro-urokinase seems comparable to other thrombolytic regimens. Reopening of occluded coronary arteries, however, is achieved relatively slowly. Thus, in its use for thrombolysis in myocardial infarction, urokinase preactivated pro-urokinase does not seem to offer superior advantages.

Coronary Angiography

Personal goals of older adults: issues in assessment and prediction.

This study identifies dimensions of individual difference in the content of older adults' personal goals and examines demographic, loss-related, and contextual influences on these goals. Results are based on the responses of 179 elders to a 112-item inventory designed to tap achievement, maintenance, disengagement, and coping goals in 16 life domains. Factor analyses yielded 10 dimensions that describe themes of global motivation, concerns about support and desired pace, and complexity of life. Demographic disadvantages and age-related transitions were related to greater desire for disengagement, support, and stability. Elders who were married and healthy were more likely to report a desire for an energetic life-style. Results are discussed in terms of implications for future research on elders' goals as a context for understanding the meaning of self-evaluation and environmental influences on aging.

Achievement

Framing the construct of life satisfaction in terms of older adults' personal goals.

Older adults' life satisfaction can be better understood in light of their personal goals. This study of 179 elders examined (a) how goals correlate with satisfaction, (b) whether elders maintain satisfaction by accommodating goals to past losses, and (c) how correlations between satisfaction and key predictors differ among groups with different goals. Satisfaction was related positively to social maintenance and energetic life-style goals and negatively to concerns for improvement, disengagement, stability, and reduced activity. Past losses were correlated with current goals but not with satisfaction, consistent with the notion of accommodation. A cluster analysis identified 5 patterns of goals: high demand, age prescribed, self-focused, socially engaged, and low demand. Correlations between satisfaction and other predictors differed by cluster, suggesting that the determinants of elders' satisfaction depend on personal goals.

Achievement

[New possibilities in diagnosing hemolytic disease of newborn infants].

The diagnosis and management of HDN relies on measurement of maternal anti-D, amniotic fluid analysis and fetal blood sampling by chordiocentesis. However, amniocentesis and chordiocentesis have substantial risks of fetomaternal hemorrhage and subsequent increase in maternal anti-D. In addition to quantitation the functional activity of maternal anti-D has been determined by measuring the interaction of red blood cells sensitized by maternal serum in monocyte-monolayer assays. We assessed the functional activity of anti-D by titration of the sensitized red blood cells using selected sera with rheumatoid factor (RF) as human anti-IgG. First experiments using monoclonal anti-D showed a good correlation between erythrophagocytosis and RF titers. The bilirubin-protein ratio in amniotic fluid may be of great value in predicting the severity of HDN, as shown in 94 cases with severe and 39 cases with moderate disease. Amniotic fluid analysis is complicated by the presence of hemoglobin; we developed a computer program to solve this problem. To improve the serological diagnosis of ABO incompatibility, we measured IgG-anti-A, B in 1,392 maternal and newborn sera applying a sensitive gel test with Coombs serum. Furthermore, we determined the hemolytic activity of anti-A, B by microscopic observation of the morphological changes of red blood cells.

Blood Transfusion, Intrauterine

[New possibilities in diagnosis of hemolytic diseases in newborns].

The diagnosis and management of the hemolytic disease of the newborn (HDN) rely on measurement of maternal anti-D, amniotic fluid analysis, and fetal blood sampling by cordocentesis. However, amniocentesis and cordocentesis have substantial risks of fetomaternal hemorrhage and subsequent increase in maternal anti-D potency. In addition to quantitation, the functional activity of maternal anti-D has been determined by measuring the interaction of red blood cells sensitized by maternal serum in monocyte-monolayer assays. We assessed the functional activity of anti-D by titration of the sensitized red blood cells using selected sera with rheumatoid factor (RF) as human anti-IgG. First experiments using monoclonal anti-D showed a good correlation between erythrophagocytosis and RF titers. The bilirubin/protein ratio in amniotic fluid may be of great value in predicting the severity of HDN, as shown in 94 cases with severe and 39 cases with moderate disease. Amniotic fluid analysis is complicated by the presence of hemoglobin; we developed a computer program to solve this problem. To improve the serological diagnosis of ABO incompatibility, we measured IgG-anti-A,B in 1,392 maternal and newborn sera applying a sensitive gel test with Coombs serum. Furthermore, we determined the hemolytic activity of anti-A,B by microscopic observation of the morphological changes of red blood cells.

ABO Blood-Group System

cDNA sequence and deduced amino acid sequence of the precursor of the 37-kDa inner envelope membrane polypeptide from spinach chloroplasts. Its transit peptide contains an amphiphilic alpha-helix as the only detectable structural element.

We present the nucleotide sequence and the deduced amino acid sequence of a cDNA clone that encodes the entire precursor of the 37-kDa inner envelope membrane protein from spinach chloroplasts. The precursor protein consists of 344 amino acids (Mr 38,976). In vitro processing followed by radiosequence analysis of the in vitro transcribed and translated precursor protein revealed that its transit peptide consists of only 21 amino acid residues. The transit peptide has the potential to form an amphiphilic alpha-helix with a strong hydrophobic moment. It is speculated that this structural element represents an ancestral envelope-targeting domain. The in vitro synthesized precursor protein is directed to the chloroplasts and it is inserted into the envelope membrane in an ATP-dependent manner. The mature protein (323 amino acid residues, Mr 36,830) has a moderate hydrophobicity and contains only one membrane-spanning segment which is located at the C-terminus and possibly anchors the protein within the envelope membrane.

Amino Acid Sequence

Jaw fractures in the County of Kopparberg and Stockholm 1979-1988. A retrospective comparative study of frequency and cause with special reference to assault.

The material comprised all 367 patients with fractured jaws treated at the Departments of Oral Surgery, Karolinska Institutet, Stockholm (216) and the Central Hospital in Falun (151) during 1979, 1982, 1985 and 1988. Manibular fractures predominated. There was no increase of the number of fractures in Stockholm and a slight decrease in Falun. In both districts the patients were predominantly men aged between 20 and 35. The most common cause of fractures in Stockholm was assault followed by traffic accidents. In Falun traffic accidents were most common, followed by assault. No increase in assaults was found. The study refutes the widespread impression of a steadily increasing incidence of cases of assault and an increasing frequency of aggravated assault.

Accidents, Traffic

[Controlled immunoglobulin therapy in immune hemolytic anemia by positive pool immunoglobulin fluorescence test].

An Italian boy with homozygous beta-thalassemia showed a shortening of transfusion intervals at the age of three years. He had a positive direct antiglobulin test (DAT) because of C3d-loaded red blood cells without any detectable erythrocytic antibody. Serologic investigations indicated a recent EBV infection. Pool immunoglobulin fluorescence test (PIT) revealed a loading of red blood cell membranes with antigens. Oral prednisone therapy did not show any effect. After a single infusion of 400 mg immunoglobulin per kg body weight decrease of hemoglobin concentration slowed down to the rate before crisis. DAT and PIT became negative. The immune hemolytic crisis was possibly due to erythrocyte loading with EBV antigen that caused activation of the alternate complement pathway. Detection of antigen loaded red blood cells by PIT suggested a immunoglobulin therapy in order to coat the structures promoting hemolysis. Thus, a positive PIT seems to be a criterion for successful application of immunoglobulins in immune hemolytic anemia.

Anemia, Hemolytic, Autoimmune

Serum testosterone (T) and 5-alpha-dihydrotestosterone (DHT) in male fallow deer (Dama dama L.): seasonality and age dependence.

1. Seasonal levels of testosterone (T) and 5-alpha-DHT (DHT) were determined by RIA in serum of seven adult male fallow deer living under outdoor conditions (Göttingen, FRG; 51.32 degrees NL). 2. The study, spread over six consecutive years, reveals the following seasonal T changes: Minimum concentrations in November or December, around antler casting and at early antler growing phase; increasing levels in the course of late antler development (mineralization) with relatively high values around velvet shedding; peak levels occurring during onset of rutting period followed by a sharp decrease after the rut; and distinct and oscillating T peaks during late winter and spring. 3. For the first time DHT levels were measured in male cervidae. Surprisingly, large values of DHT were found and occasionally levels were higher than T concentrations, but without a significant annual periodicity. 4. In some individuals maximum DHT values were found shortly before and during the rut. 5. During several months of the annual cycle individual T and DHT profiles showed opposite relationships, particularly during antler growing phase and shortly before antler casting. 6. Around rut the size of T peak levels depends on animal age.

Aging

A rapid evolution mechanism may contribute to changes in sex ratio, multiple birth incidence, frequency of auto-immune disease and frequency of birth defects in Clomid conceptions.

Under conditions favourable to the horizontal transmission of genetic material, a clomiphene isomer is hypothesized to encourage an alternate ovulatory route, with consequence for the sex ratio, multiple birth incidence, incidence of auto-immune disease, and frequency of malformations.

Abnormalities, Drug-Induced

Sequence analysis and protein import studies of an outer chloroplast envelope polypeptide.

A chloroplast outer envelope membrane protein was cloned and sequenced and from the sequence it was possible to deduce a polypeptide of 6.7 kDa. It has only one membrane-spanning region; the C terminus extends into the cytosol, whereas the N terminus is exposed to the space between the two envelope membranes. The protein was synthesized in an in vitro transcription-translation system to study its routing into isolated chloroplasts. The import studies revealed that the 6.7-kDa protein followed a different and heretofore undescribed translocation pathway in the respect that (i) it does not have a cleavable transit sequence, (ii) it does not require ATP hydrolysis for import, and (iii) protease-sensitive components that are responsible for recognition of precursor proteins destined for the inside of the chloroplasts are not involved in routing the 6.7-kDa polypeptide to the outer chloroplast envelope.

Amino Acid Sequence

[The "Eilbek capillary"--a new immune hematologic technic].

Studying RBC sedimentation in hematocrit capillaries filled with a variety of separation media (Sephacryl S-300, Ultrogel AcA22 and others) and spinned down for a short time we found some striking advantages in comparison to standard hemagglutination techniques. The scope of diagnostic procedures may be improved and broadened as far as anemias caused by autoantibodies and infections as well as hemolytic disease of the newborn--especially AB0-erythroblastosis--and pretransfusion testing are concerned.

ABO Blood-Group System

Endotoxin-induced tumor necrosis factor activity production by equine peritoneal macrophages.

A study was performed to determine whether equine macrophages produce tumor necrosis factor (TNF) activity in vitro in response to endotoxin and to study the effects of endotoxin concentration and incubation time on the amount of TNF produced. Equine peritoneal macrophages were isolated and cultured in vitro for 2, 6, 12, or 24 hr in tissue culture media containing 1) no additive (nonstimulated control), 2) endotoxin (0.5 ng/ml, 5 ng/ml, or 5 micrograms/ml), or 3) the calcium ionophore A23187 (0.95 microM). The supernatant media concentrations of TNF activity were determined by an in vitro cytotoxicity bioassay using the murine fibrosarcoma cell line WEHI 164 clone 13. At all incubation times, macrophages exposed to endotoxin produced significantly more TNF than did nonstimulated control cells (P less than 0.05). Among the three doses of endotoxin tested, there were no differences in concentrations of TNF activity in the supernatant media. The mean concentration of TNF activity in media from nonstimulated macrophages was significantly less after 24 hr incubation than after 2, 6 or 12 hr. Incubation time had no effect on TNF production by macrophages exposed to 0.5 ng/ml and 5 micrograms/ml endotoxin, but macrophages exposed to 5 ng/ml endotoxin produced significantly more TNF after 6 and 12 hr than after 2 hr. To address the reason for the decrease in TNF activity in media from nonstimulated macrophages over time, a second study was designed to determine the effect of incubation on the activity of TNF under tissue culture conditions. Human recombinant TNF was added to media that was incubated 2-24 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[Cholesterol granulomatosis of the lungs].

The cholesterol storage disease of the lung is seldom and therefore we hardly think of it. An evident diagnosis can be given only by histological examinations. 2 cases are described where during life was diagnosed a silicosis and declared as an occupational disease. Autopsy revealed cholesterol storage disease without any signs of silicosis. These findings suggest, that in cases with low occupational quartz-dust-exposure it is advisable to extend the field of diagnostic procedures.

Cholesterol

Low dose urokinase preactivated natural prourokinase for thrombolysis in acute myocardial infarction.

By inducing minimal free-fibrinolytic activity with low dose urokinase, the lag phase of prourokinase can be overcome, and the rate of thrombolysis with this substance can be strongly enhanced. The thrombolytic potency of a combination of 250,000 IU of urokinase and 2 doses of prourokinase (4.5 or 6.5 megaunits) was evaluated in an open-label, nonrandomized dose-finding study. Thirty-one patients participated. With 4.5 megaunits of prourokinase (group 1, 15 patients) patency was demonstrated angiographically at 60 minutes in 33% while with 6.5 megaunits (group II, 16 patients) 75% patency was achieved (p less than 0.01). A second angiogram recorded 24 to 36 hours after thrombolysis revealed reocclusion in 60 versus 8% of primarily patent coronary arteries (p less than 0.05). Hemostatic monitoring in both groups revealed only slight to moderate consumption of fibrinogen (-9 vs -13%), plasminogen (-29 vs -34%) and alpha 2-antiplasmin (-59 vs -63%), and an increase in D-dimers, the split products of cross-linked fibrin, to a maximum of 1.008 +/- 1.211 vs 0.547 +/- 0.684 micrograms/liter. None of these differences was significant. Bleeding complications were more frequently observed in group II (13 vs 37%) (difference not significant), but were mild and related to puncture sites, except in 1 patient with mild oozing from the gum. No major hemorrhage was observed. These results suggest that low dose urokinase preactivation enhances the thrombolytic potency of prourokinase, without affecting its high fibrin specificity. Compared to previous studies using only prourokinase, low dose urokinase preactivation reduces by 50% the prourokinase dose as required for effective thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

The triose phosphate-3-phosphoglycerate-phosphate translocator from spinach chloroplasts: nucleotide sequence of a full-length cDNA clone and import of the in vitro synthesized precursor protein into chloroplasts.

The nucleotide sequence of several cDNA clones coding for the phosphate translocator from spinach chloroplasts has been determined. The cDNA clones were selected from a lambda gt10 library prepared from poly(A)+ mRNA of spinach leaves using oligonucleotide probes modeled from amino acid sequences of tryptic peptides prepared from the isolated translocator protein. A 1439 bp insert of one of the clones codes for the entire 404 amino acid residues of the precursor protein corresponding to a mol. wt of 44,234. The full-length clone includes 21 bp at the transcribed non-coding 5' region with the ribosome initiation sequence ACAATGG, a 1212 bp coding region and 199 bp at the non-coding 3' region excluding the poly(A) tail which starts 17 bp downstream from a putative polyadenylation signal, AATAAT. According to secondary structure predictions the mature part of the chloroplast phosphate translocator exhibits high hydrophobicity and consists of at least seven membrane-spanning segments. Using plasmid-programmed wheat germ lysate the precursor protein was synthesized in vitro and could be imported into spinach chloroplasts where it is inserted into the inner envelope membrane.

Amino Acid Sequence