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K Lechner

Publications and source records attributed to K Lechner.

At least 307 records · Page 17Linked to original sources
PubMed1988

Gene for the diphtheria toxin-susceptible elongation factor 2 from Methanococcus vannielii.

Protein synthesis elongation factor 2 (EF-2) from all archaebacteria so far analysed, is susceptible to inactivation by diphtheria toxin, a property which it shares with EF-2 from the eukaryotic 8OS translation system. To resolve the structural basis of diphtheria toxin susceptibility, the structural gene for the EF-2 from an archaebacterium, Methanococcus vannielii, was cloned and its nucleotide sequence determined. It was found that (i) this gene is closely linked to that coding for elongation factor 1 alpha-(EF-1 alpha), (ii) the size of the gene product, as derived from the nucleotide sequence, lies between those for EF-2 from eukaryotes and eubacteria, (iii) it displays a higher sequence similarity to eukaryotic EF-2 than to eubacterial homologues, and (iv) the histidine residue which is modified to diphthamide and then ADP-ribosylated by diphtheria toxin is present in a sequence context similar to that of eukaryotic EF-2 but it is not conserved in eubacterial EF-G. The EF-2 gene from Methanococcus is expressed in transformed Saccharomyces cerevisiae but is not ADP-ribosylated by diphtheria toxin. This indicates that the Saccharomyces enzyme system is unable to post-translationally convert the respective histidine residue from the Methanococcus EF-2 into diphthamide.

Adenosine Diphosphate Ribose↗
PubMed1988

[Interferon therapy in hematologic neoplasms].

Interferons are new and effective agents in the treatment of various haematological neoplasias. Alpha-interferon (natural or recombinant) has a high efficacy (90% response rate) in hairy cell leukaemia. Complete remissions are, however, rare and definite cure of the disease is unlikely. Alpha-interferon induces haematological remissions in about two thirds of patients with chronic myeloid leukaemia and leads to a reduction in Philadelphia chromosome in about 40% of patients. It is uncertain, however, whether this treatment will actually prolong the life of these patients as compared with conventional treatment. Alpha-interferon has a beneficial effect in some patients with low malignant non-Hodgkin lymphomas (in particular follicular lymphomas). The response rate in myeloma is rather small (20%). Gamma-interferon is not effective in hairy cell leukaemia, non-Hodgkin lymphoma and myeloma. It is, however, of some efficacy in chronic myeloid leukaemia (the response rate in lower than with alpha-interferon) and possibly has some effect in patients with acute myeloid leukaemia and myelodysplastic syndromes. The toxicity of interferons (alpha and gamma) consists of an influenza-like syndrome during the first days of treatment. Low doses of alpha-interferon show virtually no long-term toxicity. However, bone and muscular pain is sometimes dose-limiting with intermediate doses (5 to 15 million units) of alpha-interferon.

Hematologic Diseases↗
PubMed1988

Recombinant alpha-interferon (alpha-IFN) for progressive hairy-cell leukemia (HCL): a study in previously untreated nonsplenectomized patients.

Ten nonsplenectomized patients (5 males, 5 females) with hairy-cell leukemia were treated with recombinant alpha-IFN. The median age of patients was 54 years (32-76 years). The time between diagnosis and onset of treatment ranged from 1-120 months. Initially the patients received 5 x 10(6) I.U. daily by intramuscular or subcutaneous injections for 10 weeks. Thereafter the dose of IFN was reduced to 5 x 10(6) I.U. 3 x weekly and after 6 months to 5 x 10(6) I.U. 2 x weekly for at least 6 months. The median time of patient follow-up is 23 months (4-28 months). Three complete remissions were achieved after 3-24 months and five partial remissions after 4-18 months. One patient showed improvement after 3 months, and one patient died from cerebral hemorrhage after 5 weeks. In eight of ten patients peripheral blood cell counts normalized after a median of 7 months (1.5-11 months). A marked reduction in spleen size was observed in all seven patients who had splenomegaly at study entry. Two of three patients who interrupted therapy have relapsed after 2 and 6 months. We conclude that alpha-interferon is an effective method of first-line treatment in patients with HCL.

Adult↗
PubMed1988

Deficiency of pluripotent hemopoietic progenitor cells in myelodysplastic syndromes.

Pluripotent (CFU-MIX), erythroid (BFU-E) and granulocyte/macrophage (CFU-GM) progenitor cells were examined in bone marrow (BM) from 23 patients with myelodysplastic syndromes (MDS). Patients were grouped according to the FAB classification: Refractory anemia (RA), n = 3; RA with ring sideroblasts (RARS), n = 3; RA with excess of blasts (RAEB), n = 8; RA with excess of blasts in transformation (RAEBt), n = 7; chronic myelomonocytic leukemia (CMML), n = 2. In FAB groups RA, RARS, RAEB and RAEBt CFU-GM concentrations were normal or decreased but both CMML-patients had increased CFU-GM values. Abnormal cluster growth was observed in 9 of 23 MDS-patients. BFU-E colony formation was subnormal in all cases. Mixed-colony assay values were at the lower limit of controls in one patient and decreased in the remaining 22 MDS-patients. A similar growth pattern of hemopoietic progenitor cells was observed in 19 patients with acute nonlymphocytic leukemia (ANLL), who were studied for comparison. These data suggest a quantitative or qualitative/functional defect of the pluripotent progenitor cell compartment as the major cause for the cytopenia in MDS-patients.

Aged↗
PubMed1988

Colony growth characteristics in chronic myelomonocytic leukemia.

Using cell culture studies specific in-vitro characteristics have been reported for Philadelphia chromosome positive myelogenous leukemia (Ph+ CML) and for juvenile chronic myelogenous leukemia (JCML) previously. We performed cell culture studies in four patients with chronic myelomonocytic leukemia (CMML) and demonstrated the following in-vitro features: excessively increased circulating CFU-C, while BFU-E and CFU-mix were either moderately increased or not detectable; CFU-C colony formation from CMML mononuclear cells (MNC) without addition of exogenous colony stimulating activity (CSA), even after depletion from adherent cells; failing inhibition of CMML MNC on normal BFU-E colony formation. These in-vitro characteristics point to CMML as a distinct entity. In two CMML-patients investigated CFU-C proliferation appeared to some extent inhibited by the addition of IFN-alpha, IFN-gamma and TNF-alpha to cell cultures.

Aged↗
PubMed1988

IIB von Willebrand's disease: pathogenetic and therapeutic studies.

Infusion of 1-deamino-(8-D-arginine)-vasopressin (DDAVP) into patients with IIB von Willebrand's disease (vWD) has been reported to induce thrombocytopenia. In some families with this disorder thrombocytopenia is present even in the resting state. We have investigated the basis of this chronic thrombocytopenia in one such patient by performing platelet recovery and survival studies. Increased platelet consumption was suggested by a decrease in platelet recovery (40.5%, normal 45%) and mean platelet survival (112 h, normal range 144-224 h). In addition, we have administered test infusions of DDAVP and observed the effect on bleeding time and platelet count. DDAVP caused a decrease in the median platelet count from 86 x 10(9)/l (range 30-221) to 60 x 10(9)/l (range 5-144), the individual decline in the nine subjects ranging from 12% to 84% compared to the pretreatment values. Formation of platelet aggregates was observed in all patients following DDAVP. The bleeding time was prolonged before DDAVP in all patients and lengthened further in two after the infusion. However, partial correction of the bleeding time was seen in three and normalization in one patient following DDAVP infusion. Two IIB vWD patients were treated with virus-inactivated cryoprecipitate (Ristofact). Infusion of cryoprecipitate was followed by rapid appearance of all but the largest vWF multimers in plasma and did not affect the platelet count. The bleeding time was normalized in one patient but remained prolonged in the other. In conclusion, in IIB vWD patients virus-inactivated cryoprecipitate is the treatment of choice in the case of bleeding. Infusion of DDAVP might be effective in a subset of IIB vWD patients that has yet to be characterized.

Bleeding Time↗
PubMed1988

Immunoblot analysis shows changes in factor VIII inhibitor chain specificity in factor VIII inhibitor patients over time.

We have used immunoblotting of purified factor VIII (FVIII) to determine whether or not changes in FVIII chain specificity occur during the course of an inhibitor. Serial plasma samples from 15 inhibitor patients (13 hemophilic and two spontaneous) were analyzed. Nine of the 15 antibodies, all with epitopes on the 44-kilodalton (Kd) thrombin fragment of the 92-Kd FVIII heavy chain and/or the 72-Kd thrombin fragment of the 80-Kd FVIII light chain, showed no change in FVIII chain specificity. However, six of the inhibitors analyzed showed changes in FVIII fragment specificity. Four inhibitors (three hemophilic and one spontaneous) reactive with 72-Kd thrombin fragment also became reactive with the 44-Kd thrombin fragment after an anamnestic response to FVIII infusion. Another inhibitor with epitopes on both the 54-Kd and 44-Kd thrombin fragments lost most of its reactivity with the 44-Kd fragment but retained its reactivity with the 54-Kd fragment following a FVIII infusion. The inhibitor later regained its 44-Kd-fragment reactivity but lost its 54-Kd-fragment reactivity following treatment with FEIBA, FVIII inhibitor bypassing activity. The last inhibitor studied had an antibody to either the 44-Kd fragment or to both the 44-Kd and 72-Kd fragments during anamnestic responses to FVIII. These data indicate that a FVIII inhibitor patient can potentially produce antibody to multiple areas on the FVIII molecule and that this must be taken into account in the design of specific therapeutic products.

Epitopes↗
PubMed1988

Levels of plasminogen activator inhibitor in patients with angina pectoris.

Levels of plasminogen activator inhibitor type 1 (PAI) were measured in 180 patients with angina pectoris (148 males and 32 females, age range 29 to 70 years). An age-matched normal population served as a control. PAI was determined by a functional titration assay, its activity was expressed as arbitrary units (AU). PAI levels were significantly (P less than 0.005) higher in patients with angina (24.3 +/- 10.3 AU/ml) than in normals (20.4 +/- 4.6 AU/ml). PAI levels were unrelated to sex or age in both the patient and the control groups. Plasma triglyceride levels were correlated to PAI in patients and in normals. Patients with a history of previous myocardial infarction (n = 114) had similar PAI levels as patients without infarction (24.2 +/- 11.1 AU/ml as compared to 24.4 +/- AU/ml). It is concluded that PAI levels are elevated in patients with coronary heart disease, whether myocardial infarction has taken place or not.

Adult↗
PubMed1988

T cell receptor alpha mRNA transcription in T-lymphoblastic transformation of chronic myelocytic leukemia.

Analysis at the DNA and RNA level revealed a mature genetic marker profile in a case of T type blast crisis of chronic myelocytic leukemia. T cell receptor beta chain gene rearrangement as well as T cell receptor alpha mRNA transcription was demonstrated in blasts of the malignant clone. Corresponding findings were obtained from immunological phenotyping. Blasts were found to be CD7+, CD1+, CD3+, CD4+, CD8+, and TdT- and classified as common/mature thymocytes. The presence of the breakpoint cluster region gene on chromosome 22 excluded the possibility of a second neoplastic process.

Adult↗
PubMed1987

[Home treatment in hemophilia].

88 patients with severe haemophilia (66 with haemophilia A without inhibitor, 12 with haemophilia A and inhibitor, 10 with haemophilia B) currently receive comprehensive care at the Vienna haemophilia centre. Data available at the centre and a questionnaire answered by the hemophiliacs were used in order to evaluate the current situation of home care. At present, 62 (70%) out of 88 patients receive home treatment (51 with haemophilia A without inhibitor, 5 patients with haemophilia A and inhibitor and 6 with haemophilia B). For treatment of joint and muscle bleeding mean dosages of 15.3 units/kg body weight of factor VIII concentrate, 17.0 units/kg of factor IX concentrate and 30 units/kg of FEIBA were administered by the hemophiliacs. Children and young patients required higher doses (30 and 17.4 units/kg F VIII, respectively). Two thirds of the bleeding episodes were successfully treated by a single infusion. No severe side effects were observed during home treatment. Home treatment has been widely accepted by the patients. It is regarded as a practical and safe therapy and has improved the life quality of haemophiliac patients.

Adolescent↗
PubMed1987

[Oral anticoagulant therapy--renaissance of an old therapy?].

Although the antithrombotic potential of oral anticoagulants is undisputed, bleeding complications constitute a serious problem. One of the main causes for these complications has been a lack of standardization of the prothrombin time. The introduction of the International Normalized Ratio (INR) has led to a better standardization of prothrombin time. Thus, the same level of anticoagulation can be reached using different reagents and therefore over- and undercoagulation can be avoided. Furthermore, the benefit/risk ratio can be improved by adapting the intensity of anticoagulation to the indication. The following clinical conditions are established indications for treatment with oral anticoagulants: Prevention of cardiac emboli in acute anterior myocardial infarction with atrial thrombus, in patients with atrial fibrillation with or without mitral valve disease, in patients with prosthetic heart valves and in patients with dilated cardiomyopathy. Furthermore, oral anticoagulants should be given to patients after femoropopliteal bypass. A relatively mild oral anticoagulant treatment (INR 2-3) is sufficient to prevent recurrences of venous thrombosis and pulmonary emboli. The duration of treatment in patients with venous thromboembolism depends on some clinical features and the results of clotting tests which indicate an increased tendency to thrombosis.

Administration, Oral↗
PubMed1987

[Right heart failure as a clinical sign of pulmonary artery sarcoma].

A 43 year-old female patient was admitted on account of severe dyspnoea of several months' duration and thrombocytopenia. The clinical symptomatology was compatible with pulmonary embolism, but no source of embolization was found and heparin therapy did not lead to clinical improvement. Angiography of the pulmonary artery revealed multiple filling defects. Symptoms improved after treatment with cortisone and so a malignant process was assumed. The patient died from right ventricular failure before the diagnosis could be established. At autopsy a sarcoma of the pulmonary artery, obviously originating from the pulmonary trunk was found. Thrombocytopenia most probably resulted from consumption of platelets by a mechanism corresponding to the Kasabach-Merritt syndrome. The difficulties in the diagnosis of pulmonary artery sarcomas are discussed and the 69 previously published cases are reviewed.

Adult↗
PubMed1987

Haemolytic transfusion reactions due to HLA antibodies. A prospective study combining red-cell serology with investigations of chromium-51-labelled red-cell kinetics.

In a prospective study to see whether HLA sensitisation is associated with increased red-blood-cell (RBC) destruction after HLA-incompatible transfusion, chromium-51-labelled RBC survival and site of sequestration were monitored in nine patients in whom HLA antibodies had developed after RBC transfusions. The donors selected were compatible in ABO and RBC-specific antigen systems but mismatched for the HLA antigen in question. Haemolytic transfusion reactions occurred in all four patients who received HLA-B7-incompatible RBC. A direct radioimmune anti-IgG test became positive, Cr51-RBC survival was very short (22.3, 36.9, 41.4, and 44.0 days), and excess sequestration in the spleen was measured. There was a rise in serum lactic dehydrogenase and a fall in haptoglobin. HLA-B7 antibody was detected in the eluate prepared from RBC collected after transfusion. A similar reaction was found in only one further patient, caused by an HLA-A2 incompatibility. No indications of immune-mediated RBC sequestration were discernible after transfusion of HLA-B7-compatible RBC in one of the patients who had shown a reaction with HLA-B7-incompatible blood, nor in any of the other patients who received HLA-B7-compatible RBC. The haemolytic transfusion reactions could not be anticipated by conventional crossmatch procedures, nor by the measurement of the Cr51-RBC survival 1 h after transfusion.

Aged↗
PubMed1987

[Use of genetic technics in medical diagnosis exemplified by hemophilia A].

Recent years have seen the rapid development of molecular probes for the detection of defective human genes. These react either directly with the gene in question or with a DNA sequence which lies in close proximity to the gene and which exhibits polymorphism. In the case of haemophilia A two probes were found that belong to the latter category. We have used one of these probes to test its usefulness in the detection of carriers of haemophilia A. For these tests DNA was isolated from blood cells, but can, in principle, be obtained just as easily from other cells or tissues. The results of tests on several families show that the gene technological method is much more precise and sensitive than conventional methods used so far to detect carriers. In all cases a clear assertion was possible as to whether or not the person in question was a carrier of haemophilia A. The method should be applicable to prenatal diagnosis.

DNA↗
PubMed1987

Incidence of inhibitors in patients with severe and moderate hemophilia A treated with factor VIII concentrates.

Recent data published on the prevalence of inhibitors to factor VIII in hemophiliacs on treatment show great variations, with prevalence rates ranging from 3.6 to 14.2%. We have studied the cumulative risk of inhibitor development in a cohort of 62 patients with hemophilia A. All patients were born after 1960, were natives of the Vienna area, had a factor VIII activity of less than 5%, and were treated at least once. Using the method of Cutler and Ederer, the cumulative risk of inhibitor development was found to be 24% at the age of 25 years. Most inhibitors developed between the ages of 3 and 7 years. The current prevalence of F VIII inhibitors in the group of patients studied is 17.5%. It is concluded that prevalence data underestimate the true risk of inhibitor development.

Adult↗
PubMed1987

Pregnancy and delivery after bone marrow transplantation (BMT) for severe aplastic anemia (SAA). A case report.

A 23 years old multiple pretransfused female with severe aplastic anemia (SAA) underwent bone marrow transplantation (BMT). Cyclophosphamide (200 mg/kg) was used for conditioning, donor buffy coat cells were given as rejection prophylaxis. Seven months after BMT regular menses started in the absence of exogenous hormonal manipulation and 21 months after BMT the patient became pregnant. Pregnancy was complicated by mumps in the 14th week. It was terminated at term by cesarean section. The normally developed newborn girl (3,450 gm) presented with a "persistent fetal circulation syndrome". After surgical correction of the patent ductus arteriosus Botalli the girl baby recovered quickly.

Adult↗