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H Braunsteiner

Publications and source records attributed to H Braunsteiner.

At least 55 records · Page 3Linked to original sources
PubMed1991

[In vitro effects and possible clinical relevance of interleukin 3].

Cytokines are mainly produced by monocytes and lymphocytes and influence a broad spectrum of physiological processes within the hematopoietic and the immune system. Clinical trials have mainly been initiated with a subgroup of cytokines namely the hematopoietic growth factors. Interleukin 3 (IL-3) was recently introduced into phase I and II trials. This factor was also termed "multipoietin" because of its ability to stimulate in vitro the hematopoietic stem cell and thus all three hematopoietic cell lines. The latest in vivo data, however, demonstrate that IL-3 stimulates leukopoiesis and megakaryopoieis with only marginal effects on erythropoiesis. In large clinical trials the therapeutic effect of this factor is investigated in patients with myelodysplastic syndromes. Further indications will be other primary bone marrow failures and aplasia caused by bone marrow transplantation, aggressive chemotherapy and radiation. Potential applications offered by combinations with other cytokines can hardly be foreseen.

Animals↗
PubMed1991

[Cerebrovascular disorders as a manifestation of a generalized disease].

During the last years several risk factors for cerebrovascular disease (CVI) could be identified by epidemiologic studies; the incidence of CVI, like that of coronary artery disease, seems to be closely related to high blood pressure, hyperlipidaemia, smoking and diabetes mellitus. The diagnostic difficulties in CVI, especially concerning the localization and size of vascular lesions, explain controversal results in the evaluation of different clinical studies. A comparison of these results is often hard to perform also out of the different statistical methods applied in the various trials. The development of improved diagnostic methods, especially ultrasonography, which allow a better definition of disease processes, offers an advantage for controlled screening and intervention trials. After all further improvements in disease prevention as well as in diagnostic and therapeutic procedures require an intensive co-operation between internal medicine and neurology.

Cardiovascular Diseases↗
PubMed1991

[Risk factors for coronary heart disease].

Cardiovascular disease remains the major cause of death in the industrialized world with dyslipidemia, hypertension and cigarette smoking leading a long list of risk factors. Recently, controversy arose from some critical articles expressing concern about the evaluation and interpretation of statistical data of epidemiologic studies. One study using covariance analysis reported an absence of the widely accepted negative association between coronary heart disease (CHD) and high density lipoprotein (HDL) cholesterol. Also criticism was expressed regarding the cost-effectiveness of preventive measures such as the use of lipid lowering drugs on life expectancy. Because of such recent scientific controversy and discussions already taking place in the media, we have summarized in this article recent epidemiologic evidence including a meta-analysis of the major epidemiologic studies on HDL. We have directed particular attention to 3 large epidemiological studies, i.e., the Familial Atherosclerosis Treatment Study (FATS), the Program on the Surgical Control of the Hyperlipidemias (POSCH), and the Cholesterol Lowering Atherosclerosis Study (CLAS), all of which have clearly demonstrated a desirable effect of intensive lipid lowering therapy on coronary lesions.

Austria↗
PubMed1991

[Hematopoietic growth factors].

Hematopoietic growth factors represent a subgroup of the cytokines and are also called colony-stimulating factors (CSFs) because of their effects in bone marrow culture. These glycoproteins are produced by a large number of cells and serve to transmit signals within the hematopoietic and the immune system either by themselves or by inducing the production and the release of other cytokines. As their genes have been cloned by molecular biology in the last year, these "recombinant" factors can be produced in large amounts for clinical trials. Cytokines make possible completely new therapy concepts by enabling medicine both to intervene in and modulate the body's own physiological processes. Therapy studies conducted with hematopoietic growth factors to date are encouraging and mostly demonstrate only tolerable dose-dependent side effects. In contrast to the maximal tolerable dose usually applied for cytotoxic therapy regimens, this "biological therapy" aims to a minimal effective dose, known e.g. from interferon. The following article will attempt to provide an insight into the first results of clinical trials and in future possibilities in the clinical application of these factors.

Animals↗
PubMed1990

[Pathogenesis of liver disease in alpha 1-antitrypsin deficiency].

Alpha-1-antitrypsin deficiency (A1ATD) is one of the most common lethal hereditary disorders. Approximately 5 to 10% of the general population carry an "at risk" gene for the development of liver disease or emphysema of the lung. Patients with A1ATD associated liver disease constitute a histologically and clinically heterogeneous group. The pathogenesis of the disease still remains to be elucidated. Recent experimental evidence produced in the transgenic mouse model is in favour of the engorgement hypothesis considering the deposition of amorphous A1AT in the hepatocytes the prime event causing liver disease. This theory, however, fails to explain the clinical observation of the presence of a number of other factors known to cause chronic liver disease in A1ATD patients. The latter observation is in support of the deficiency theory, which explains the pathogenesis of emphysema of the lung, and would point to A1ATD as a predisposition to acquire chronic disease. The meaning of the increased synthesis of stress proteins in patients with liver disease is still speculative.

Genetic Carrier Screening↗
PubMed1989

In vitro human polymorphonuclear leukocyte chemokinesis and human monocyte chemotaxis are different activities of aminoterminal and carboxyterminal substance P.

Polymorphonuclear leukocytes (PMNL) are a component of the inflammatory response to neurogenic mediators. Using the micropore filter approach, the authors studied the chemoattracting properties of tachykinins, including substance P (SP), neurokinin A (NKA) and neurokinin B (NKB), and that of calcitonin gene-related peptide (CGRP) for human PMNL in vitro and now show that SP in near nanomolar concentrations stimulates locomotion of human PMNL. Locomotion of PMNL is induced by SP, aminoterminal SP (1-9) and the SP receptor antagonist [D-pro2, D-trp7,9]-SP (DPDT) but not by carboxyterminal SP (3-11), NKA, NKB, or CGRP suggesting that the aminoterminal amino acids arginine and proline are essential residues of SP in activation of PMNL locomotion. In contrast, the migratory effect of SP on monocytes resides in the carboxyterminal SP amino acid sequence, which is in agreement with carboxyterminal, SP receptor-mediated chemotaxis of human monocytes previously shown by others. From the known structure-activity relationships for SP receptors it is concluded that induction of PMNL migration by SP does not involve neurokinin-1 (NK-1), NK-2 or NK-3 receptors. "Checkerboard" analysis reveals that PMNL locomotion by SP is not dependent on concentration gradients and thus represents chemokinesis, which is enhancement of speed and/or frequency of locomotion. One cannot exclude that this action of SP on PMNL is mediated by the aminoterminal sequence via yet unknown SP "receptors".(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitonin Gene-Related Peptide↗
PubMed1989

Combination effects of human recombinant interferon (alpha-2-arg, gamma) and cytotoxic agents on colony formation of human melanoma and hypernephroma cell lines.

Malignant melanoma and hypernephroma show marginal response to chemotherapeutics and interferons when used as single agents. Using a modified soft agar clonogenic assay we investigated the antiproliferative effects of combinations of vinblastine, bleomycin, adriamycin, interferon alpha and gamma. On the hypernephroma cell line combinations of bleomycin and adriamycin with interferon gamma as well as combinations of both interferon types resulted in a synergistic antiproliferative effect. On the melanoma cell line combinations of bleomycin and adriamycin with interferon alpha and combinations of vinblastine with interferon gamma acted in a synergistic manner. All other combinations tested were only additive. Thus far, we could not find any antagonistic effect of interferons and chemotherapeutics.

Antineoplastic Agents↗
PubMed1989

Abnormal megakaryopoiesis in patients with myelodysplastic syndromes: analysis of cellular and humoral defects.

In 13 patients with myelodysplastic syndrome (MDS) mature and immature erythropoietic (CFU-E, BFU-E), granulopoietic (CFU-GM) and megakaryopoietic (CFU-Meg) colony formation from human bone marrow mononuclear cells was evaluated in a microagar culture system. All but three patients exhibited abnormal CFU-Meg. The defect of CFU-Meg paralleled the reduction of BFU-E, whereas CFU-GM number declined to a lesser extent. Not only the CFU-Meg number, but also the number of megakaryocytes (Mk) per colony was reduced suggesting an additional functional CFU-Meg defect. Megakaryocytic growth factor (Meg-CSF) abnormalities in MDS patients were detected using normal nonadherent T-lymphocyte depleted bone marrow cells as target cells for serum testing. Even for sera from patients with a reduction of platelets and bone marrow megakaryocytes Meg-CSF levels were not increased. No cellular or humoral inhibition could be detected in an MDS patient with a 5q- karyotype, who had an isolated defect of the megakaryocytic cell lineage at presentation. Some patients revealed a spontaneous formation of mixed erythrocytic, granulocytic and megakaryocytic clusters in the presence of fetal calf serum or autologous patient serum, probably representing autonomous proliferation of the malignant clone. In conclusion, both cellular and humoral factors can cause abnormalities of the megakaryocytic cell lineage in MDS patients.

Adult↗
PubMed1989

Risk factors for coronary artery disease: a study comparing hypercholesterolaemia and hypertriglyceridaemia in angiographically characterized patients.

Fifty-two male patients undergoing coronary angiography were allocated to four groups each consisting of 13 subjects: group I had normal coronary arteries and patients in groups II-IV exhibited coronary artery disease. In group II, plasma cholesterol was below 250 mg dl-1 and triglycerides below 160 mg dl-1; in group III, cholesterol was above 270 mg dl-1 and triglycerides under 160 mg dl-1; and in group IV, cholesterol was under 270 mg dl-1 and triglycerides above 180 mg dl-1. The hypertriglyceridaemic group IV had the highest coronary score. In addition, it had lowest lipoprotein lipase activity, lowest HDL-cholesterol and lowest high-density lipoproteins-2 (HDL-2) levels, suggesting that this type of hypertriglyceridaemia is caused--at least in part--by lipoprotein lipase deficiency with impaired removal of the triglyceride-rich lipoproteins and increased catabolism of HDL-2. Our findings point towards a type of hypertriglyceridaemia strongly associated with coronary artery disease which should therefore be treated accordingly.

Adult↗
PubMed1988

Neuromodulation by polypeptide growth factors: preliminary results on the distribution of epidermal growth factor receptors in adult brain.

Polypeptide growth factors and their receptors are expressed within the brain and neuromodulatory functions are described. Using autoradiography of 125I-epidermal growth factor (EGF) and radioimmunohistochemistry with an antibody to the EGF receptor, we have determined the distribution pattern of the EGF receptor in adult rat brain. The patterns achieved by both methods were similar at every level of the neuroaxis examined. Highest densities of autoradiographic grains were present in the cingulate cortex, cerebral cortex, hippocampus, amygdala and caudate putamen. This pattern of distribution suggests that EGF may have neuromodulatory functions. Common expression of polypeptide receptors by cells of different organ systems constitutes a biochemical basis for homeostatic network regulation.

Animals↗
PubMed1988

Effects of biosynthetic human proinsulin on plasma lipids in type 2 diabetes mellitus.

Plasma cholesterol, triglycerides, HDL2-cholesterol, and HDL3-cholesterol were studied in 18 patients with Type 2 diabetes. Prior to entering the clinical trial, the study subjects were in stable control under a fixed mixture of 20% regular and 80% NPH (isophane) biosynthetic human insulin twice daily. The patients were randomized to treatment with either biosynthetic human proinsulin or biosynthetic human NPH insulin (controls) twice daily. Glucose control was kept constant in both groups throughout the study. Of the nine patients treated with proinsulin, eight exhibited a decrease of plasma triglycerides (median decrease by 0.13 mmol/l). In contrast, all nine controls showed a rise (median increase by 0.69 mmol/l) of plasma triglycerides (p less than 0.001). In keeping with the fall of plasma triglycerides, HDL2-cholesterol rose in all but one proinsulin-treated patients. Both treatment modalities reduced HDL3-cholesterol with a median decrease of 0.20 mmol/l (p less than 0.01) with proinsulin and 0.26 mmol/l with NPH insulin (p less than 0.05). We conclude that human proinsulin is able to reduce plasma triglycerides and to increase HDL2-cholesterol in the majority of patients with Type 2 diabetes and thus appears to alter favourably risk factors for coronary heart disease.

Aged↗
PubMed1988

[Effects of intensified insulin therapy on fat metabolism in type 1 diabetes mellitus].

The effect on fat metabolism of an intensified insulin treatment regimen was tested in 23 type I diabetics and compared with that of conventional insulin treatment. Definite improvement in blood glucose levels was found after a one-year intensified treatment schedule (HbA1 of 8.1% under intensified treatment, compared with 10.6% under conventional treatment). The intensified treatment schedule also resulted in a significant reduction in plasma triglycerides from an average of 114 mg/dl to 94 mg/dl (p less than 0.05), at the same time the plasma HDL-cholesterol levels increased. Plasma concentrations of total cholesterol and LDL-cholesterol remained unchanged. Thus intensified insulin treatment was shown to improve glucose metabolism, lower HDL-cholesterol and in this way improve the risk profile for macroangiopathy.

Adolescent↗
PubMed1988

[Normalization of perinatal morbidity in gestational diabetes by strict metabolic adjustment].

A prospective study compared the perinatal morbidity of 141 normal pregnancies (group I) with that of 108 pregnancies in whom gestational diabetes had been treated early (group II) and 35 with unsatisfactorily treated gestational diabetes (group III). The therapeutic goal in gestational diabetes was to have a postprandial blood-glucose level of less than 130 mg/100 ml. If this was not achievable through diet alone, insulin was injected once daily. Neonatal macrosomia, dystrophy, acidosis, hyperbilirubinaemia, hypoglycaemia and hypocalcaemia had a normal incidence in group II, but in group III macrosomia was twice as frequent as in group II (P less than 0.02), and acidosis (pH less than 7.20) twice as frequent (P less than 0.05). The results indicate that strict metabolic control in gestational pregnancy will achieve a normal rate of perinatal morbidity.

Apgar Score↗
PubMed1988

Proliferation and differentiation of human erythropoiesis in vitro: effect of different human lipoprotein species.

In order to permit erythroid proliferation in agar, a serum-free system was developed based on McCoy's 5A medium at pH 8.0, containing deionized and delipidated bovine serum albumin, iron-saturated transferrin, and crude erythropoietin (step III). Addition of the entire complement of serum lipoproteins, termed lipoprotein fraction I (density, less than 1.21 g/ml), increased the number of erythroid colony-forming units and erythroid burst-forming units to numbers indistinguishable from those observed with media containing serum. Moreover, terminal differentiation occurred to fully hemoglobinized normoblasts and even mature erythrocytes. Under these conditions, the erythropoietin dose-response curve obtained when not using serum was comparable to that with serum. Colony formation also displayed a linear relationship to seeding densities down to limiting dilutions. For differential analysis of the main density lipoprotein fractions, sequential ultracentrifugation was performed to isolate very low-density lipoproteins, low-density lipoproteins (LDL), high-density lipoproteins2 (HDL2), and HDL3, which were then added individually to serum-free cultures. Of the main lipoprotein classes, LDL exhibited the most proliferative capacity, followed by HDL2 and HDL3. Our findings indicate that when serum is substituted by well defined compounds including highly purified lipoprotein fractions, a serum-like proliferation and differentiation of human erythropoietic progenitor cells in agar can be obtained.

Bone Marrow↗
PubMed1987

[Experience using bone marrow transplantation in the treatment of hematologic neoplasms and solid tumors].

Between October 1983 and October 1985, 12 allogeneic bone marrow transplantations from HLA-identical siblings were performed for treatment of malignant disease (11 haemopoietic malignancies) or severe aplastic anaemia (1 case). All patients showed prompt and complete engraftment of donor cells on average around day 17 after transplantation. 10 patients are alive and well 50-760 days after transplantation, without any signs of recurrence and partly without immunosuppressive therapy. Two patients died, one due to relapse of the leukaemia, and one as a result of CMV interstitial pneumonia. Graft versus host disease was seen in 6 of the 12 patients. Additional immunosuppressive therapy was necessary in 4 of them. The incidence of idiopathic interstitial pneumonia in our group of patients was low (two cases). Also tested was an experimental protocol for the treatment of chemotherapy-resistant metastatic solid tumours. After removal of all clinically detectable tumour tissue by maximal surgical therapy in 5 patients, residual systemic metastases were treated by means of total body irradiation and high-dose cyclophosphamide, followed by autologous bone marrow transplantation with curative intention. Relapse occurred in 4 patients between day 100 and 720 after BMT bone marrow transplantation. Only one patient remains without sign of relapse.

Adult↗
PubMed1987

Changes of the phenotype of erythroid progenitor cells (BFU-E, CFU-E) and their progenies during early steps of differentiation.

Early differentiation processes of human erythroid progenitor cells (BFU-e, CFU-e) have been studied during in vitro proliferation using a panel of monoclonal antibodies with known reactivity on different levels of the erythroid cell line. Two antibodies recognizing structures on BFU-e (VIP-2b, BMA 021), two antibodies reactive with CFU-e and nucleated red cells (5F1, CLB-Ery-3) and one antibody directed against glycophorin A (VIE-G4) were used for this study. Normal human bone marrow cells were induced to proliferation in an erythroid progenitor cell assay and, after different periods of incubation, agar cultures were treated with these antibodies and complement. Thereafter, the remaining erythroid cells were incubated again to continue their proliferation with the same stimulators as before. The changes of the phenotype of BFU-e and CFU-e progenies during in vitro proliferation were determined by the reduction of colony formation in comparison with untreated control cultures. Our results indicate that the loss of HLA-DR antigens and the p45 structure is accompanied by the acquisition of structures recognized by the antibodies 5F1 and CLB-Ery-3. After 5-7 d of incubation BFU-e derived progenies exhibit the same antigenic structure as has been found for CFU-e. Glycophorin A expression could only be demonstrated at a late differentiation stage of the erythroid cell lineage.

Antibodies, Monoclonal↗