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K Hager

Publications and source records attributed to K Hager.

31 records · Page 2Linked to original sources
PubMed1992

High-density lipoprotein-mediated lysis of trypanosomes.

Nearly 90 years after the discovery that certain African trypanosornes were killed by normal human serum, we still do not understand how this innate trypanocidal factor works. Biochemical studies have provided us with an unlikely candidate: human high-density lipoprotein (HDL). This trypanosome lytic factor (TLF) from human serum is important since its activity restricts the host range of Trypanosoma brucei brucei, and the expression of this natural killing factor in cattle would represent a novel approach to the control of bovine tryponosomiasis. Here, Steve Hajduk, Kristin Hager and Jeffrey Esko discuss evidence for the TLF being a minor subclass of serum HDL and propose a mechanism for lysis based on the binding, endocytosis and lysosomal targeting of TLF.

Journal Article↗
PubMed1992

Molecular biology of African trypanosomes: development of new strategies to combat an old disease.

African trypanosomes are protozoan parasites that cause a number of diseases of man and domesticated animals in large regions of sub-Saharan Africa. The diseases have proven to be particularly difficult to prevent or to effectively treat due to features of both the trypanosome and the insect vector, the tsetse fly. The habitat of the tsetse and its resistance to insecticides have rendered vector control efforts ineffective. Attempts to develop a vaccine against the African trypanosomes has been dwarfed by the parasite's ability to change the composition of its exposed surface antigens. This process of antigenic variation allows the parasite to avoid the host's immune response and presents the host with a seemingly endless antigenic repertoire. Since conventional approaches to the control of African trypanosomiasis have largely met with failure, there has been a renewed interest in identifying novel aspects of the biology, biochemistry, and molecular biology of trypanosomes that might be exploited to develop new targets for vaccines or chemotherapy. Importantly, this research has opened a virtual Pandora's box of exciting biochemical and molecular surprises, which makes the African trypanosomes not only important medical pathogens but also an exciting experimental system for the basic scientist. In this review, the authors will describe some of the most recent and intriguing developments in the field of molecular parasitology.

Animals↗
PubMed1992

The Na+/glucose cotransporter (SGLT1).

An important class of Na+ transport proteins is the cotransporters. They exist in bacteria and animal cells and are responsible for the "active" accumulation of sugars, amino acids, carboxylic acids and some ions, e.g., I-, Cl-, and PO-4, in cells. In the small intestine and renal proximal tubule the cotransporters play an important role in the transport of salt and water across the epithelia. The most well known and best characterized Na+ cotransporter is the intestinal brush border Na+/glucose cotransporter. We have cloned, sequenced, and expressed both the rabbit and human Na+/glucose cotransporters. The cDNAs code for 73kDa proteins with 662-664 residues (86% identity). Secondary structure analysis suggests a 12 membrane-spanning helical model with the N- and C-termini in the cytoplasm. A single N-linked glycosylation site is utilized at Asn248. These sugars are not required for function. Two essential residues for functional expression in oocytes have been identified, Asp28 and Arg300. In two sisters with glucose-galactose malabsorption the transport defect is caused by a missense mutation changing Asp28 to Asn28, and we have found that changing Arg300 to Cys300 eliminated transport. Current research is directed to finding residues and domains essential for ligand binding and transport, and we are using electrophysiological techniques to correlate structure and function.

Amino Acid Sequence↗
PubMed1990

Effect of gemfibrozil on erythrocyte membrane lipids in geriatric patients.

Twenty geriatric patients with primary or secondary hyperlipidemia and suffering from various other diseases received for three weeks once daily 900 mg gemfibrozil. The hyperlipidemia had not been treated before, and a cholesterol-reduced diet did not succeed in lowering total cholesterol below 6.75 mmol/l (260 mg/100 ml) and serum triglycerides below 1.97 mmol/l (175 mg/100 ml). The purpose of this study was to analyze the lipid composition of the erythrocyte membrane, serum lipids and rheological parameters before and after the therapy. Mean serum total cholesterol and triglyceride content decreased significantly by 16.3% (p less than 0.05) and 35.2% (p less than 0.01) on average, respectively. Aggregation of thrombocytes and of erythrocytes, thrombin time and partial thromboplastin time slightly varied during the three weeks' treatment, but without statistical significance. The content of total long-chain saturated fatty acids in the phospholipid fraction of the erythrocyte membrane decreased slightly from 41.3% to 40.9% (p less than 0.05), whereas the total w6-unsaturated fatty acids without the precursor linoleic acid increased by about the same extent from 15.66% to 16.0% (p less than 0.05). The molar ratio of phospholipid to cholesterol content decreased significantly (p less than 0.01) due to a reduced phospholipid content at the end of the therapy. In conclusion, in addition to reducing the serum lipids, gemfibrozil slightly effects the lipid composition of erythrocytes, but the effects of the varied concentrations of long-chain saturated and long-chain w6-unsaturated fatty acids in the phospholipid fraction on membrane fluidity might be compensated, at least partly, by the decrease of the ratio of membrane phospholipid to cholesterol.

Aged↗
PubMed1988

Clearance of heterologous, homologous and damaged homologous erythrocytes by the isolated perfused rat liver.

Homologous and autologous rat erythrocytes, human erythrocytes as well as glutaraldehyde-treated and hemolysed homologous red blood cells suspended in an isotonic, buffered saline, free of immunoglobulins were perfused through the isolated rat liver. The mononuclear phagocyte system of the liver (mainly Kupffer cells) was able to recognize damaged rat and heterologous human erythrocytes and to sequester them by a direct membrane-erythrocyte mechanism. Hemoglobin and homologous and autologous rat erythrocytes were not sequestered or only to a minor extent. High sequestration rates are reflected by an increased energy demand with subsequent increase of the lactate-pyruvate and beta-hydroxybutyrate-acetoacetate-quotient.

Animals↗
PubMed1987

[Thrombocytes and aging. Protein and neuraminic acid content of thrombocytes of male donors of various age groups].

Thrombocytes of male donors of different age groups were investigated in terms of their content of N-acetylneuraminic acid (NANA) and protein. For this purpose NANA was split up hydrolytically as well as enzymatically by neuraminidase. Furthermore, the relation of NANA to protein was determined in the lysed thrombocytes of these donors. A significant increase in the protein content of platelets could be observed between group I and III (young and old donors). The relation of NANA to protein (acid hydrolysis) existing between these groups decreased significantly with growing age. Appropriate results could also be attained after having made a separate analysis in lysed thrombocytes. The results achieved allow the conclusion to be drawn that there is a changed thrombocytopoiesis in men of old age.

Adult↗
PubMed1985

Aging in vivo and neuraminidase treatment of rat erythrocytes and their sequestration by the isolated perfused rat liver.

The isolated perfused rat liver as a model for phagocytosis leaves the specific arrangement of macrophages in the original tissue structure intact. Therefore phagocytosis may occur under terms closely approaching physiological conditions. Separation of rat erythrocytes according to their density in 13% young, 75% mature and 12% old cells permits the establishment of differences in the mean cellular volume (MCV), mean cellular hemoglobin concentration (MCHC) and content of N-acetylneuraminic acid per red blood cell (NANA/RBC). Perfusion of these fractions does not result in significant differences of sequestration of the isolated liver. Enzymatic release of 90% of membrane-bound sialic acid causes a significant increase of 20% in the elimination of erythrocytes from the perfusate. Treatment with neuraminidase is a trigger for sequestration either by adherence or by complete phagocytosis. Incubation of neuraminidase-treated erythrocytes with plasma does not increase the removal rate of cells during perfusion.

Animals↗
PubMed1981

[A computerized questionnaire to the anaesthetic record (author's transl)].

To the Anaesthetic Record of the Kreiskrankenhaus Donaueschingen a questionnaire was developed and used during te years 1978 and 1979 to compute the yearly reports of the whole anesthesia department as well as for each anesthesia resident. The various anaesthetics and techniques formed the basis of our data retrieval program. The questionnaire allows the computation of the annual reports in a simple and time saving way. Only one punch card is used; the rate of error is small. Since coding can be done by the anaesthesist himself or the nurse anaesthesist, no additional coding personnel is required.

Anesthesia↗
PubMedDate not supplied

Blood coagulation factors in the elderly.

To investigate causes of the age-dependent increase of thromboembolic events, plasma coagulation parameters were determined in healthy elderly blood donors in comparison with young, and elderly diseased blood donors. Partial thromboplastin and thrombin clotting times were slightly shortened, whereas prothrombin and reptilase clotting times were unaltered. Plasma concentration of clotting factors like F I, VII, VIII: C, X, HMW-kininogen and prekallikrein were increased, whereas the coagulation inhibitor antithrombin III was decreased. Concerning fibrinolysis, plasminogen and alpha-2-antiplasmin were not affected by age, but plasminogen activators in the euglobulin fraction were lower. This shift in the pattern of coagulation factors favors enhanced fibrin formation and delayed fibrinolysis in the elderly. Higher intermediary products demonstrate that activation of coagulation and fibrinolysis happen more often in elderly healthy people. Together with blood stasis and vessel wall damage, this shift of the hemostatic balance contributes to a higher incidence of thromboembolic disorders in the aged.

Aging↗
PubMedDate not supplied

Age dependency of the sialic acid content of fibrinogen. Consequences for erythrocyte aggregation.

Sialic acid (SA) content of plasma proteins and fibrinogen was investigated in 60 persons of different age and health status. SA/mg fibrin rose with age and morbidity in plasma, rinsed clots of fibrin from plasma and after prothrombin adsorption as well as in fibrin clots prepared from purified fibrinogen. The higher plasma SA is caused by increasing concentrations of glycoproteins like fibrinogen, but also by a higher content of SA/mg protein, as has been shown for fibrinogen. SA is considered to be an unspecific marker of acute phase reactions. Changing SA content of glycoproteins may have functional consequences. An increased red cell aggregation with fibrinogen of healthy elderly correlated with its SA content, but SA is most probably only indicating an altered protein heterogeneity in the aged and not a causative factor that influences erythrocyte aggregation.

Journal Article↗
PubMedDate not supplied

Interleukin-6 and selected plasma proteins in healthy persons of different ages.

In the present study, interleukin-6 (IL-6) and several acute phase proteins were measured in healthy participants (23-87 years of age). A linear correlation between IL-6 and age was established with an increase of 0.016 pg/ml (0.004) per year of life. Whereas CRP remained below 0.5 mg/dl in all participants, an increase with age for fibrinogen and an inverse relation for albumin as well as transferrin were obtained. However, the increase of IL-6 did not correlate with any of these changes. IL-6 associated diseases may therefore occur more often with advancing age, but in healthy participants IL-6 does not explain the changing plasma protein pattern resembling that of an acute phase reaction.

Acute-Phase Proteins↗
PubMedDate not supplied

Rehabilitation of the elderly - influence of age, sex, main diagnosis and activities of daily living (ADL) on the elderly patients' return to their previous living conditions.

In geriatric rehabilitation, discharge to the living conditions in which elderly patients lived before admission is one of the most important treatment goals. The objective of this study therefore was to determine the extent to which this criterion was influenced by age, sex, main diagnosis and activities of daily living. For that purpose the results of 1845 patients, admitted consecutively from 1993 to 1995 were analysed. With advancing age an increasing number of patients was unable to return to their previous living conditions (10% vs. 24% comparing the age groups '64 years and younger' versus '85 years and older'). This age-associated decline was present for both sexes and for several diagnosis groups. A low (0-40 points) ADL-score on admission was found to be associated with a significantly smaller percentage of patients returning home (75%) than a high (90-135 points) score (95%). The criteria sex and main diagnosis were not significantly linked with the return home. According to multiple regression analysis, ADL-score on admission was the only parameter found to be significantly associated with return to preadmission living conditions, but not age. But if the ADL-score at discharge was added to the regression analysis, this criterion proved to be the only predictor. Despite the negative correlations between age as well as ADL-score on admission with return home and due to the fact that nearly three quarters of the oldest patients and of those most severely impaired on admission were able to return to their previous living conditions it seems worthwhile not to exclude patients only because of their age or the initial degree of dependence on care alone from rehabilitation services.

Journal Article↗