PubMed Health⌕ Search

Biomedical subjects

M Köhler

Publications and source records attributed to M Köhler.

At least 91 records · Page 5Linked to original sources
PubMed1998

Genomic organization and chromosomal localization of the interphotoreceptor matrix proteoglycan-1 (IMPG1) gene: a candidate for 6q-linked retinopathies.

The interphotoreceptor matrix is a unique extracellular matrix occupying the space between the photoreceptors and the retinal pigment epithelium. Due to its putative function in the maintenance and integrity of the photoreceptor cells, it is conceivable that it is involved in retinal degeneration processes. More recently, a novel gene encoding a 150-kDa interphotoreceptor matrix proteoglycan, designated IMPG1, was cloned and shown to be expressed in both rod and cone photoreceptor cells. To assess this gene in human retinal dystrophies, we have now determined the genomic organization and chromosome location of IMPG1. It is composed of 17 exons ranging from 21 to 533 bp, including an alternatively spliced exon 2. Using somatic cell hybrid mapping and FISH analysis, we have assigned the IMPG1 locus to 6q13-->q15. As this interval overlaps with the chromosomal loci of several human retinopathies, including autosomal dominant Stargardt-like macular dystrophy (STGD3), progressive bifocal chorioretinal atrophy (PBCRA), and North Carolina macular dystrophy (MCDR1), IMPG1 represents an attractive candidate for these 6q-linked disorders.

Alternative Splicing↗
PubMed1998

Evaluation of the GTI-ASP-1 platelet antigen genotyping kit for the determination of the HPA-1 genotype.

The human platelet antigen system HPA-1 is involved in most cases of neonatal alloimmune thrombocytopenia and posttransfusion purpura, and occasionally causes refractoriness to platelet transfusions. Complete concordance was obtained in genotyping for HPA-1 in all samples tested with the HPA-1 genotyping kit and a ligation-based typing method. However, the genotyping kit is less sensitive than ligation- based typing, which could be of importance when testing cells from amnionic fluid or from chorionic villi.

Journal Article↗
PubMed1998

Quality and safety of platelet apheresis concentrates produced with a new leukocyte reduction system.

OBJECTIVES: Contaminating white blood cells (WBC) in apheresis platelet concentrates (PC) can cause a variety of adverse effects after platelet transfusion. To obtain PCs with low WBC contamination, a new leukoreduction system (LRS) utilizing 'fluidized particle bed' technology has recently been introduced. METHODS: We prospectively examined the effect of LRS apheresis on the donor, the quality of the resulting PCs (n = 120), and the platelet increment in the corresponding recipients. Conventionally prepared apheresis PCs served as control group (n = 27). Platelet glycoproteins were examined by flow cytometry. RESULTS: In LRS apheresis, we observed no serious adverse effects on the donors, but the postdonation absolute lymphocyte counts were reduced from 1,787 +/- 505/microliter to 1,405 +/- 383/microliter (p < 0.001). Comparable results were seen in non-LRS donors. The collection efficiency of the LRS procedures was 50.0 +/- 7.6%, resulting in a yield of 4.3 +/- 1.0 x 10(11) platelets/PC. In flow cytometry, platelet glycoproteins in LRS PCs were not elevated: mean fluorescence of CD62 (6 +/- 4) or CD63 (9 +/- 3) in comparison with non-LRS PCs (mean fluorescence of CD62: 7 +/- 4, CD63: 8 +/- 3). Median leukocyte contamination of the LRS PCs was 0.41 x 10(5) (range 0.07-8.5) WBCs/unit. In 43 recipients, the 24-hour corrected count increments after transfusion of LRS PCs (12,530 +/- 8,761) were essentially the same as those of 20 recipients of non-LRS PCs (13,133 +/- 9,812; p = 0.75). CONCLUSIONS: LRS apheresis appears to be a safe procedure, which produced effective PCs with few contaminating leukocytes. With new apheresis technology, filtration of PCs may become superfluous.

Antigens, Human Platelet↗
PubMed1998

Thromboembolic complications associated with the use of prothrombin complex and factor IX concentrates.

In 1994, shortly after a heat-treated prothrombin complex concentrate (PCC) had been withdrawn from the German market due to transmission of hepatitis B, the license of another brand was withdrawn, due to 3 acute fatalities associated with the use of this product. We report on the clinical data of altogether 5 patients, who died during a 3 month period in Germany after having received this brand of PCC. All patients had surgery, acquired deficiencies of coagulation factors, and underlying diseases predisposing for thrombosis or disseminated intravascular coagulation. PCC was administered for the prevention of bleeding. In three patients, a drug interaction of PCC with aprotinin may also have played a role. Several points, however, are suspicious of a major causative effect of the respective product, (a) the close temporal correlation between administration of the drug and the subsequent clinical as well as laboratory deterioration, (b) the accumulation of these adverse events in a short period of time, when the use and market share of this brand increased due to the shortage of other products, and (c) laboratory abnormalities of this brand which have been consistently observed in several in vitro studies.

Adult↗
PubMed1997

Mutations in the human factor XII gene.

The factor XII gene from 31 unrelated factor XII-deficient patients from Germany, Switzerland, and Austria was screened for mutations at the genomic level. Several novel mutations were detected and their absence in a control group of 74 healthy unrelated individuals was checked. Most changes are in the serine protease domain affecting the catalytic triad His-393-Asp-442-Ser-544; two missense mutations, R398Q (arginine 398 to glutamine; gene bank accession no. U71276) and L395M (leucine 395 to methionine; gene bank accession no. U71277), are close to the active site histidine at position 393. Another mutation detected in a cross-reacting material (CRM)-positive female with a history of three abortions affects the active site aspartic acid by changing it to asparagine (D442N; gene bank accession no. U71275). The novel mutation G570R (glycine 570 to arginine; gene bank accession no. U71274) giving rise to a CRM-positive phenotype is located next to Cys571, which forms a vital disulfide bridge. Two mutations are causing reading frame shifts: one single basepair deletion in exon 12 [exon 12: 10590(DelC); gene bank accession no. U71278] and one acceptor splice site mutation [exon 14: 11397(G --> A); gene bank accession no. L43615]. The putative regulatory mutation exon 1:-8 (g --> c) in the upstream region of the gene is associated with an aberrant Taq I restriction site allele in intron B of the gene (gene bank accession no. X80393).

Alleles↗
PubMed1997

Cloning of two novel human importin-alpha subunits and analysis of the expression pattern of the importin-alpha protein family.

The import of many proteins into the nucleus is mediated by the importin-alpha/beta heterodimer. While only one importin-beta gene has been found, several forms of importin-alpha have been described. In addition to the three human importin-alphas already identified, we report here the primary structure of two new human importin-alpha proteins. The five known human importin-alpha subunits can be classified into three subfamilies that appear conserved in higher eukaryotic organisms. We show by immunoblotting that the different importin-alpha subfamilies are expressed in a variety of human tissues and mammalian cell lines.

Amino Acid Sequence↗
PubMed1997

Ape-like or hominid-like? The positional behavior of Oreopithecus bambolii reconsidered.

Comparative morphological and functional analyses of the skeletal remains of Oreopithecus bambolii, a hominoid from the Miocene Mediterranean island of Tuscany-Sardinia (Italy), provides evidence that bipedal activities made up a significant part of the positional behavior of this primate. The mosaic pattern of its postcranial morphology is to some degree convergent with that of Australopithecus and functionally intermediate between apes and early hominids. Some unique traits could have been selected only under insular conditions where the absence of predators and the limitation of trophic resources play a crucial role in mammalian evolution.

Animals↗
PubMed1997

Parallel changes in nuclear and cytosolic calcium in mouse pancreatic beta-cells.

In the neuroendocrine pancreatic beta-cell, elevations in intracellular Ca2+ lead to insulin secretion and the initiation of gene transcription. However, the relationship between cytosolic and nuclear Ca2+ in these cells is unknown. The Ca2+ permeability of the nuclear membrane would therefore determine if Ca2+ could play a direct role in Ca2+-dependent nuclear processes. Using confocal fluorescence microscopy with the ratiometric Ca2+ indicator indo-1 and carefully correcting for compartmentalized indicator, we now demonstrate that there is no difference between the nuclear Ca2+ concentration and the cytosolic Ca2+ concentration ([Ca2+]c) in the resting beta-cell. Slow Ca2+ oscillations induced by glucose, fast oscillations induced by glucagon-like peptide-1 and responses to potassium and carbachol all indicate that changes in cytosolic Ca2+ are reflected within the nucleus. We conclude that there are no restrictions on Ca2+ entry into the nucleus of the pancreatic beta-cell subsequent to increases in [Ca2+]c. This implies that any signal involved in increasing [Ca2+]c, and thereby insulin release, may also promote nuclear Ca2+-induced gene transcription.

Animals↗
PubMed1997

[Formation, therapy and prevention of false aneurysm of the femoral artery following diagnostic and interventional heart catheterization].

OBJECTIVE: As pseudoaneurysm of the femoral artery after catheter introduction is a frequent complication, its causes and therapeutic options were investigated in a large patient collective. PATIENTS AND METHODS: In a prospective study with colour-Doppler duplex sonography of 6928 patients after diagnostic and of 3764 after interventional cardiac catheterisation, pseudoaneurysms were diagnosed in 80 patients (0.75%), 46 after diagnostic (0.66%) and 34 after interventional (0.9%) catheterisation. RESULTS: The incidence was higher in women than men (1.33% vs 0.58%; P < 0.05). Anticoagulation after sheath removal was the leading risk factor (n = 55, 68.8%), especially after interventional coronary intervention 85.3 vs 56.5%, P < 0.05). Local compression under duplex sonography monitoring was undertaken in 69 patients (86.3%), achieving aneurysmal obliteration in 53 (76.8%). Spontaneous thrombosis occurred in 15 of the remaining 27 patients, and surgical closure became necessary in 12. CONCLUSIONS: These data indicate a risk profile for the occurrence of pseudoaneurysm after cardiac catheterisation which can be dealt with by preventive measures. Local compression under duplex sonographic monitoring was the treatment of choice with a high success rate and low incidence of complications.

Aged↗
PubMed1997

Frequency and causes of refractoriness in multiply transfused patients.

The use of leukocyte-depleted blood components has become the standard therapy for multiply transfused patients during the past few years, as a measure to reduce the frequency of alloimmunization and refractoriness. We assessed frequency and causes of refractoriness, defined as a repeated 24-h post-transfusion platelet count below 20,000/microliters, in 145 consecutive patients who received three or more single-donor platelet concentrates during a 1-year period. Flow-cytometric detection of anti-platelet antibodies and a glycoprotein-specific ELISA were applied for the diagnosis of alloimmunization. Forty patients (27.6%) had at least one episode of refractoriness. In 25 of these 40 patients (62.5%), nonimmune factors (fever, sepsis, coagulopathy, splenomegaly) alone were the cause. In 15 refractory patients alloantibodies were detected. In seven patients (17.5%), alloimmunization alone caused an inadequate transfusion response, while in eight refractory patients (20.0%) alloimmunization and fever or sepsis were present. HLA antibodies were detected in 17 patients (11.7%); three patients (2%) had platelet-specific antibodies in addition to HLA antibodies; in two patients panreactive platelet antibodies were detectable. All 17 patients had a history of previous transfusions or pregnancy. We did not observe primary immunization in patients transfused exclusively with filtered (leukodepleted) blood products. Our data suggest that alloimmunization in patients with a negative risk history can be prevented by the exclusive use of leukodepleted blood components.

Antigens, Human Platelet↗
PubMed1997

[Incidence and therapy of peripheral arterial vascular complications after heart catheter examinations].

We analyzed the incidence and management of major vascular complications at the arterial puncture site following diagnostic or interventional cardiac catheterization. 27387 cardiac catheterization procedures were performed for diagnostic (n = 19581) or interventional (n = 7806) purposes at our institution during a 7-year study period. A total number of 114 major vascular complications (0.42%) were identified. In 36 (0.13%) patients an arterial occlusion at the puncture site was detected, 34 patients (0.12%) had severe hematoma (blood transfusion or surgical repair necessary), 32 patients (0.12%) developed false aneurysms, 9 patients (0.03%) with av-fistulas and 3 patients (0.01%) had other complications. The following factors were predictive for a significant increase in the incidence of major vascular complications: Female gender, interventional catheterization using larger introducer sheaths and necessitating effective perioperative doses of heparine, and peripheral vascular disease. Operative repair was necessary in 62 patients (54%), 34 patients (30%) were treated conservatively. In 18 patients (17%) acute vascular occlusion could be managed by percutaneous transluminal balloon dilatation and intravascular thrombolysis of the obstruction, in 3 patients additional stent-implantation was necessary in the presence of a large occlusive dissection. Overall the rate of clinically significant major vascular complications is low. In the future a greater number of vascular complications at the entry site for cardiac catheterization will be treated with nonoperative methods (e.g. manual compression of pseudoaneurysms or catheter-based techniques for recanalization of acutely occluded vessels.

Adult↗
PubMed1997

Interpretation of multiple Q(0,0) bands in the absorption spectrum of Mg-mesoporphyrin embedded in horseradish peroxidase.

Mg-mesoporphyrin horseradish peroxidase (MgMP-HRP) and MgMP-HRP complexed with naphtohydroxamic acid (NHA) have been studied by fluorescence line narrowing (FLN) and pressure tuning spectral hole burning (SHB) techniques. In each sample, the low temperature absorption spectra show more than one transition in the origin range of the Q band. Comparisons with broad-band fluorescence spectra and FLN studies suggest that the multiple band feature originates from the presence of different configurations of the metal-porphyrin that are subject to Qx-Qy splitting within the protein cavity. This suggestion is supported by pressure tuning SHB studies. In the uncomplexed as well as in the NHA-complexed form of MgMP-HRP, irradiation in the Q band produces photoproduct bands, which has been attributed to a species with smaller Qx-Qy splitting. In an amorphous matrix, on the other hand, only one form of MgMP could be found, and no splitting could be observed. The binding of NHA does not significantly alter the bulk parameters of the protein matrix, but it reduces the structural variety in the configuration of MgMP to a single form with a more distorted structure and thus with an enlarged Qx-Qy splitting.

Horseradish Peroxidase↗
PubMed1997

Sedation and analgesia for colonoscopy: patient tolerance, pain, and cardiorespiratory parameters.

BACKGROUND: Colonoscopy is generally performed with the patient sedated and receiving analgesics. However, the benefit of the most often used combination of intravenous midazolam and pethidine on patient tolerance and pain and its cardiorespiratory risk have not been fully defined. METHODS: In this double-blind prospective study, 150 outpatients undergoing routine colonoscopy were randomly assigned to receive either (1) low-dose midazolam (35 micrograms/kg) and pethidine (700 micrograms/kg in 48 patients, 500 micrograms/kg in 102 patients), (2) midazolam and placebo pethidine, or (3) pethidine and placebo midazolam. RESULTS: Tolerance (visual analog scale, 0 to 100 points: 0 = excellent; 100 = unbearable) did not improve significantly more in group 1 compared with group 2 (7 points; 95% confidence interval [-2-17]) and group 3 (2 points; 95% confidence interval [-7-12]). Similarly, pain was not significantly improved in group 1 as compared with the other groups. Male gender (p < 0.001) and shorter duration of the procedure (p = 0.004), but not amnesia, were associated with better patient tolerance and less pain. Patient satisfaction was similar in all groups. Oxygen desaturation and hypotension occurred in 33% and 11%, respectively, with a similar frequency in all three groups. CONCLUSIONS: In this study, the combination of low-dose midazolam and pethidine does not improve patient tolerance and lessen pain during colonoscopy as compared with either drug given alone. When applying low-dose midazolam, oxygen desaturation and hypotension do not occur more often after combined use of both drugs. For the individual patient, sedation and analgesia should be based on the endoscopist's clinical judgement.

Adult↗
PubMed1997

Prestorage inline filtration of whole blood for obtaining white cell-reduced blood components.

BACKGROUND: Preliminary studies have indicated that the inline filtration of whole blood is a feasible method of obtaining white cell (WBC)-reduced packaged red cells (RBCs) and WBC-reduced fresh-frozen plasma (FFP) while using only one filter. STUDY DESIGN AND METHODS: An inline WBC-reduction filter, specially designed for this purpose and integrated in a "top-top" system, was used in the preparation of 24 units of WBC-reduced RBCs (RBC-F) and FFP (FFP-F) in each of two transfusion centers (Vienna and Göttingen). Twelve conventionally prepared units of RBCs (RBC-C) and FFP (FFP-C) served as controls. WBC contamination was assessed in each unit with the Nageotte chamber. Several coagulation measures were evaluated by using standardized test systems. RESULTS: The median WBC contamination in RBC-F was 27,000 per unit in Vienna and 50,000 in Göttingen. In FFP-F, the median WBC contamination was 13,000 (Vienna) and 31,000 (Göttingen) per unit. Coagulation factors I, V, VIII, and XI in FFP-F were not different from those in FFP-C. In addition, markers for the activation of coagulation and fibrinolysis--that is, factor XIIa, prothrombin fragments, thrombin-antithrombin complexes and fibrinogen degradation products--were not greater in FFP-F. CONCLUSION: Blood components prepared from inline-filtered whole blood meet the standards for WBC-reduced RBCs and FFP. The protein profile of FFP-F is not altered, and markers for the activation of coagulation and fibrinolysis show no increase.

Blood Coagulation Factors↗