PubMed Health⌕ Search

Biomedical subjects

H Mader

Publications and source records attributed to H Mader.

17 recordsLinked to original sources
PubMed1999

Extended recombinant bacterial ghost system.

Controlled expression of cloned PhiX174 gene E in Gram-negative bacteria results in lysis of the bacteria by formation of an E-specific transmembrane tunnel structure built through the cell envelope complex. Bacterial ghosts from a variety of bacteria are used as non-living candidate vaccines. In the recombinant ghost system, foreign proteins are attached on the inside of the inner membrane as fusions with specific anchor sequences. Ghosts have a sealed periplasmic space and the export of proteins into this space vastly extends the capacity of ghosts or recombinant ghosts to function as carriers of foreign antigens. In addition, S-layer proteins forming shell-like self assembly structures can be expressed in candidate vaccine strains prior to E-mediated lysis. Such recombinant S-layer proteins carrying foreign epitopes further extend the possibilities of ghosts as carriers of foreign epitopes. As ghosts have inherent adjuvant properties, they can be used as adjuvants in combination with subunit vaccines. Subunits or other ligands can also be coupled to matrixes like dextran which are used to fill the internal lumen of ghosts. Oral, aerogenic or parenteral immunization of experimental animals with recombinant ghosts induced specific humoral and cellular immune responses against bacterial and target components including protective mucosal immunity. The most relevant advantage of recombinant bacterial ghosts as immunogens is that no inactivation procedures that denature relevant immunogenic determinants are employed in this production. This fact explains the superior quality of ghosts when compared to other inactivated vaccines. The endotoxic component of the outer membrane does not limit the use of ghosts as vaccine candidates but triggers the release of several potent immunoregulatory cytokines. As carriers, there is no limitation in the size of foreign antigens that can be inserted in the membrane and the capacity of all spaces including the membranes, peri-plasma and internal lumen of the ghosts can be fully utilized. This extended recombinant ghost system represents a new strategy for adjuvant free combination vaccines.

Adjuvants, Immunologic↗
PubMed1999

New strategies for combination vaccines based on the extended recombinant bacterial ghost system.

Controlled expression of cloned PhiX174 gene E in Gram-negative bacteria results in lysis of the bacteria by formation of an E-specific transmembrane tunnel structure built through the cell envelope complex. Bacterial ghosts have been produced from a great variety of bacteria and are used as non-living candidate vaccines. In the recombinant ghost system, foreign proteins are attached on the inside of the inner membrane as fusions with specific anchor sequences. Ghosts have a sealed periplasmic space and the export of proteins into this space vastly extents the capacity of ghosts or recombinant ghosts to function as carriers of foreign antigens, immunomodulators or other substances. In addition, S-layer proteins forming shell-like self assembly structures can be expressed in bacterial candidate vaccine strains prior to E-mediated lysis. Such recombinant S-layer proteins carrying inserts of foreign epitopes of up to 600 amino acids within the flexible surface loop areas of the S-layer further extend the possibilities of ghosts as carriers of foreign epitopes. As ghosts do not need the addition of adjuvants to induce immunity in experimental animals they can also be used as carriers or targeting vehicles or as adjuvants in combination with subunit vaccines. Matrixes like dextran which can be used to fill the internal lumen of ghosts can be substituted with various ligands to bind the subunit or other materials of interest. Oral, aerogenic or parenteral immunization of experimental animals with recombinant ghosts induced specific humoral and cellular immune responses against bacterial and target components including protective mucosal immunity. The most relevant advantage of ghosts and recombinant bacterial ghosts as immunogens is that no inactivation procedures that denature relevant immunogenic determinants are employed in the production of ghosts. This fact explains the superior quality of ghosts when compared to other inactivated vaccines. As carriers of foreign antigens there is no limitation in the size of foreign antigens to be inserted and the capacity of all spaces including the membranes, periplasma and internal lumen of the ghosts can be fully utilized. Using the different building blocks and combining them into the recombinant ghost system represents a new strategy for adjuvant free combination vaccines.

Adjuvants, Immunologic↗
PubMed1997

Self and Polar Foreign Gas Line Broadening and Frequency Shifting of CH3F: Effect of the Speed Dependence Observed by Millimeter-Wave Coherent Transients

The shape of the (J, K: 2, 1 <-- 1, 1) millimeter line of CH3F in collision with polar buffer molecules has been investigated in the temperature range 140-300 K. The experiments exploit a Stark switching coherent transient technique, namely the optical free precession phenomenon, the Fourier transform of which is the usual steady state absorption lineshape. Using various buffer gases (CH3Br, CH3F, and NH3), the observed time domain signals provide the first experimental evidence in the millimeter range that line broadenings as well as frequency shiftings depend on the relative speed of collision partners; that is, lineshapes can become narrowed and asymmetric according to the molecular mass ratio and the type of collisional interaction involved. The experimental signals are analyzed with a time domain speed-dependent Voigt profile: for the polar buffer molecules considered, it is shown that a simultaneous interpretation of the broadening and narrowing parameters as well as of their temperature dependence can be satisfactorily obtained only with a realistic collision theory; in contrast with atomic buffer gases, velocity changing collisions play a negligible role. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗
PubMed1997

Bacterial ghosts as multifunctional vaccine particles.

Expression of cloned PhiX174 gene E in Gram-negative bacteria results in lysis of the bacteria by formation of an E-specific transmembrane tunnel structure built through the cell envelope complex. Bacterial ghosts have been produced from a variety of bacteria including Escherichia coli. Salmonella typhimurium, Salmonella enteritidis, Vibrio cholerae, Klebsiella pneumoniae, Actinobacillus pleuropneumoniae, Haemophilus influenzae, Pasteurella haemolytica, Pasteurella multocida, and Helicobacter pylori. Such ghosts are used as non-living candidate vaccines and represent an alternative to heat or chemically inactivated bacteria. In recombinant ghosts, foreign proteins can be inserted into the inner membrane prior to E-mediated lysis via specific N-, or C-, or N- and C-terminal anchor sequences. The export of proteins into the periplasmic space or the expression of recombinant S-layer proteins vastly extents the capacity of ghosts or recombinant ghosts as carriers of foreign epitopes or proteins. Oral, aerogenic or parenteral applications of (recombinant) ghosts in experimental animals induced specific humoral and cellular immune responses against bacterial and target components including protective mucosal immunity. The most relevant advantage of ghosts and recombinant bacterial ghosts as immunogens is that no inactivation procedures that denature relevant immunogenic determinants are employed in the production of ghosts used as vaccines or as carriers of relevant antigens. The inserted target antigens into the inner membrane or into S-layer proteins are not limited in size.

Adjuvants, Immunologic↗
PubMed1996

Bacterial ghosts: non-living candidate vaccines.

Expression of cloned PhiX174 gene E in bacteria results in lysis of bacteria. It is unique among phage lysis systems as it introduces a transmembrane tunnel structure through the cell envelope complex of Gram-negative bacteria. The resulting bacterial ghosts have intact envelope structures devoid of cytoplasmic contents. E-mediated lysis has been achieved in a variety of Gram-negative bacteria including Escherichia coli, Salmonella typhimurium, Vibrio cholerae, Klebsiella pneumoniae, and Actinobacillus pleuropneumoniae. Such ghosts, derived from human or animal pathogens, have been proposed as non-living candidate vaccines and represent an alternative to heat or chemically inactivated bacteria. In 'recombinant ghosts', foreign proteins (e.g., viral proteins) are inserted into the inner membrane via specific N-, or C-, or N- and C-terminal anchor sequences prior to lysis. Relevant advantages of (recombinant) bacterial ghosts as immunogens include: (i) inactivation procedures that denature relevant immunogenic determinants are not employed in the production of ghosts used as vaccines or as carriers of relevant antigens; (ii) the recombinant proteins are inserted into a highly immune stimulatory environment; (iii) there is no size limitation of the foreign protein moieties: multiple antigenic determinants can be presented simultaneously; (iv) bacterial ghosts can be produced inexpensively in large quantities; (v) (recombinant) ghosts are stable for long periods of time and do not require the cold chain storage system. Intraperitoneal, subcutaneous or intramuscular applications of recombinant ghosts in experimental animals induced specific humoral and cellular immune responses against bacterial and viral components. Initial aerosol vaccinations of swine with ghosts from Actinobacillus pleuropneumoniae showed that protective immunity can be established by this route of application and that the well-preserved surface structures of ghosts obtained by E-mediated lysis are able to target the mucosal immune system.

Animals↗
PubMed1992

31P magnetic resonance spectroscopy in dilated cardiomyopathy and coronary artery disease. Altered cardiac high-energy phosphate metabolism in heart failure.

BACKGROUND: The purpose of this work was to further define the value of cardiac 31P magnetic resonance (MR) spectroscopy for patients with coronary artery disease and dilated cardiomyopathy. METHODS AND RESULTS: Blood-corrected and T1-corrected 31P MR spectra of anteroseptal myocardium were obtained at rest using image-selected in vivo spectroscopy localization, a selected volume of 85 +/- 12 cm3, and a field strength of 1.5 T. Nineteen volunteers had a creatine phosphate (CP)/ATP ratio of 1.95 +/- 0.45 (mean +/- SD) and a PDE/ATP ratio of 1.06 +/- 0.53; in four patients with left anterior descending coronary artery (LAD) stenosis, six patients with chronic anterior wall infarction, and four patients with chronic posterior wall infarction, CP/ATP and phosphodiester (PDE)/ATP ratios did not differ from those in volunteers. Twenty-five measurements of 19 patients with dilated cardiomyopathy yielded a CP/ATP of 1.78 +/- 0.51 and a PDE/ATP of 0.98 +/- 0.56 (p = NS versus volunteers). When these patients were grouped according to the severity of heart failure, however, CP/ATP was 1.94 +/- 0.43 in mild (p = NS versus volunteers) and 1.44 +/- 0.52 in severe DCM (p < 0.05), respectively. No correlation was found between CP/ATP and left ventricular ejection fraction or fractional shortening, but correlation of CP/ATP with the New York Heart Association (NYHA) class was significant (r = 0.60, p < 0.005). Six patients with dilated cardiomyopathy were studied repeatedly before and after 12 +/- 6 weeks of drug treatment leading to clinical recompensation with improvement of the NYHA status by 0.8 +/- 0.3 classes. Concomitantly, CP/ATP increased from 1.51 +/- 0.32 to 2.15 +/- 0.27 (p < 0.01), whereas PDE/ATP did not change significantly. CONCLUSIONS: Cardiac high-energy phosphate metabolism at rest is normal in LAD stenosis and chronic myocardial infarction in the absence of heart failure. The CP/ATP ratio has low specificity for the diagnosis of dilated cardiomyopathy. However, CP/ATP correlated with the clinical severity of heart failure and may improve during clinical recompensation.

Adult↗
PubMed1991

Impact of bovine somatotropin on dairying in eastern Europe.

Milk production of dairy cows in six herds was increased by approximately 15% by the administration of recombinantly derived bST in a sustained-release vehicle (somidobove, Eli Lilly/Elanco, Indianapolis, IN) at 28-d intervals, which commenced at 52 to 104 d postpartum. Milk composition, acidity, flavor, and growth of commercial lactic acid starter cultures were unaffected by somidobove treatment. No adverse effect upon health (metabolic diseases, mastitis) and reproduction was noted. Blood glucose, FFA, aspartate aminotransferase, alanine aminotransferase, Ca, Na, and K were unaffected by the application of somidobove. Somidobove did not affect the appearance of the organs of cows at slaughter; however, somidobove-treated cows had less subcutaneous and omental adipose tissue than controls. Cultured explants of subcutaneous adipose tissue of treated cows showed significantly lower lipogenesis from acetate than controls. The release of FFA was not affected by treatment. Recombinantly derived somidobove has been judged in Czechoslovakia to be effective and safe for cows and the environment. Edible products from the treated cows are safe for human consumption.

Adipose Tissue↗
PubMed1982

Diminished response of ovarian cAMP to luteinizing hormone in experimental uremia.

In prepuberal female rats with acute bilateral nephrectomy or chronic subtotal nephrectomy, the increase of ovarian cAMP concentration in response to submaximal doses of luteinizing hormone (LH 10 micrograms) and human chorionic gonadotropine (hCG 2.5 IU) was diminished (CO + 2.5 IU hCG 488 +/- 49 pmoles cAMP/mg protein; NX + 2.5 IU hCG 366 +/- 56. P less than 0.05). The cAMP response to follicle stimulating hormone (FSH) was unchanged. The abnormality was found both after administration of LH in vivo and incubation of ovaries with LH in vitro. Similarly, plasma estradiol concentrations in response to submaximal hCG stimulation were diminished. Basal cAMP concentrations and cAMP concentrations after maximal stimulation were unchanged. The defect was observed both in ovaries of untreated prepuberal rats, of pregnant mare serum (PMS)-treated rats (follicular phase) and PMS/hCG-treated rats (luteal phase). Diminished ovarian cAMP response to LH was observed both in parathyroid intact and in parathyroidectomized rats. Administration of 1,25(OH)2D3 in physiological doses (60 ng/kg) to acutely uremic rats restored diminished ovarian cAMP response to submaximal LH stimulation irrespective of parathyroid status. The effect of 1,25(OH)2D3 could not be reproduced by hypercalcemia resulting from intraperitoneal calcium injection. In vivo administration of indomethacin further diminished ovarian cAMP response in uremic animals and had no effect in control animals. Incubation of ovaries with PGE1 and PGE2 increased basal and stimulated cAMP concentrations and abolished the difference between control and uremic animals. The diminished response of ovarian cAMP content to submaximal doses of hCG was not corrected by bromocriptine (1 mg/kg) despite normalization of hyperprolactinemia. The present study shows diminished ovarian cAMP and plasma estradiol response to LH in experimental uremia. It documents a role of 1,25(OH)2D3 and prostaglandins in the genesis of this abnormality.

Alprostadil↗
PubMed1982

[Fe-, Cu-, Zn-, Ni- and Mn-concentrations in sow's milk during a five-week lactation period].

In a trial with 18 sows of the German landrace in three groups the dietary copper supply was varied in gravidity and lactation. Iron, copper, zinc, nickel and manganese concentration of milk was measured on 11 different days during the five weeks' lactation period in response to alimentary copper supply. Copper supply did not influence iron, zinc, and manganese concentration even if it was deficient during gravidity and lactation. Mature sow's milk contained 1.2 micrograms Fe, 1.5 micrograms Cu, 6-8 micrograms Zn, 0.16-0.23 microgram Ni and 0.07-0.13 microgram Mn per g fresh milk. First colostrum contained higher copper and zinc concentrations and lower concentrations of nickel and manganese compared to mature milk. Fe concentration remained constant. This investigation reproduced and completed thereby previous results. It was concluded that in copper deficiency status the interactions of copper with iron, zinc, nickel and manganese may not be effective for the excretion pathway milk.

Animals↗
PubMed1980

[The influence of ceruloplasmin injections on the Cu- and Fe-metabolism of piglets].

In two experiments with a total of 56 piglets the influence of intravenous injections of ceruloplasmin (CP) on the 2nd and 4th day of their lives on criteria of the Cu- and Fe-metabolism was investigated. Due to the injections, the CP-activities and the Cu-concentration in the plasma increased, as a rule, more than in the untreated control animals. This effect was more distinct and longer recognisable after the injections on the 2nd day of life. Effects on the Fe-metabolism registered in a increased Fe-concentration in the plasma. Hemoglobin content, number of erythrocytes as well as the activities of blood catalase were in no case influenced by the injections.

Animals↗
PubMed1978

Treatment with essential amino acids in patients on chronic hemodialysis: a double blind cross-over study.

Patients on chronic hemodialysis may suffer from a latent protein deficiency, and therapy with essential amino acids has been recommended. In a double blind cross-over study, 13 hemodialysis patients received orally 15.7 g of essential amino acids daily over a 3-month period. Patients were on a liberal diet, containing 1 g of protein per kilogram of body weight per day. Hemodialysis was adequate. Therapy resulted in an increase in urea, uric acid, C3 c complement factor and a fall in C4. Lysine levels increased and phenylalanine fell. Malnutrition could not account for the observed metabolic changes, which are more likely due to uremic metabolic disturbances. A liberal diet of 1 g of protein per kilogram of body weight appears sufficient for patients on hemodialysis. Treatment with essential amino acids offers no advantage.

Adult↗
PubMed1976

[Utilization of xylitol in the isolation-perfused myocardium of the rat].

1. In the rat heart muscle, only 3 to 4% of the oxygen-consumption can be referred to xylitol utilization. With xylitol as only substrate the heart is working under substrate deficiency conditions. 2. Diabetes mellitus does not improve the xylitol utilization in the rat heart muscle. 3. The data are compared with the activities of xylitol degrading enzymes in the heart muscle.

Animals↗