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Biomedical subjects

H Bayer

Publications and source records attributed to H Bayer.

At least 19 recordsLinked to original sources

Relationship between serum concentrations of interleukin-6 and tumor necrosis factor alpha in female Turkish subjects with normal and impaired glucose tolerance.

Serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFalpha) concentrations were measured in subjects during two-hour glucose loading in order to investigate the effects of glucose on serum IL-6 and TNFalpha concentrations. Twenty-six female subjects (mean age 60 +/- 10 years) had normal glucose tolerance (NGT) and nineteen female subjects (mean age: 63 +/- 9 years) had impaired glucose tolerance (IGT) according to WHO criteria. Serum IL-6 and TNFalpha concentrations were measured by chemiluminescent immunometric assay. Subjects with IGT have higher fasting serum TNFalpha levels than subjects with NGT (p < 0.01). Serum IL-6 and TNFalpha concentrations were elevated during glucose loading (for each comparison, p < 0.01). The increase in serum TNFalpha concentrations in IGT was greater than in NGT (p < 0.01). Serum IL-6 and TNFalpha concentration significantly correlated with insulin and glucose in IGT group (for each comparison, p < 0.01). The correlation between serum glucose and cytokines concentrations was significant in IGT (for each comparison, p < 0.01). There was also a positive correlation between serum IL-6 and TNFalpha in NGT and IGT (for each comparison, p < 0.01). In conclusion, hyperglycemia is associated with increased circulating cytokine concentrations and fasting TNFalpha concentrations seem to be more associated with IGT than IL-6.

Aged↗

A new side stream process for easily degradable industrial waste waters to avoid sludge bulking.

A new treatment scheme for the treatment of easily biodegradable industrial waste waters has been developed. The side stream treatment of dairy waste water with the excess sludge from the domestic treatment line of the regional treatment plant Bad Vöslau has been operated successfully for a period of three years during which the industrial load stemming from the dairy increased from 800 kg COD/d to 2,500 kg COD/d with peak loads up to 5,000 kg/d. Despite of the increased load to the treatment plant the total aeration tank volume had not been increased. This treatment is performed in an existing aeration tank of the WWTP (V = 1,800 m3) which is now used as contact tank for the combined aeration of dairy waste water and excess sludge from the domestic treatment line (volume aeration tank = 15,000 m3). In this tank the easily degradable substrate from the industrial waste is mainly adsorbed to the biological sludge and after a mechanical dewatering transferred to the anaerobic digester where it yields in an increased gas production. The filtrate of the dewatering process is completely free from biodegradable material and can without danger of bulking be fed to the aeration tank of the domestic treatment line. The new process has proven to be extremely flexible since already now daily peak loads exceeding the design load by more then 60% could be treated in the plant without any problems. Compared to other alternatives for the dairy waste water treatment that were investigated during this study, the new side stream process is very advantageous. No other pre-treatment process for industrial waste water could have been operated under comparable loading conditions without severe operating problems.

Austria↗

'No-show' for initial screening at a community mental health centre: rate, reasons and further help-seeking.

INTRODUCTION: The aim of this study was to investigate aspects of the phenomenon of 'no-show' for initial screening in a community mental health centre (CMHC). First, the 'no-show' rate was assessed and possible differences between the 'show' and 'no-show' populations were studied. The 'no-show' individuals were then approached to ask about their reasons for their no-show and about any subsequent help seeking. METHODS: Included in this study were all adults referred to the Maastricht CMHC between December 1995 and April 1997. The 'no-show' rate was assessed for the referrals in 1996. In May 1997 a brief questionnaire, concerning the 'no-show' reason and further help-seeking was sent to all 202 individuals who failed to keep the first appointment in the 15-month period. RESULTS: The 'no-show' rate in 1996 was 9.6% (165 out of 1716 individuals). The most prevalent reasons for 'no-show' were the waiting list, lack of motivation and resolution of the mental health problem. The presenting complaint was still present in 78.7% of the 'no-show' subjects. Most of them had received treatment from their GP, social worker or a private practice. Despite persistence of their problem, 29% didn't seek further treatment. An equal number of subjects solved their problem before the screening interview. CONCLUSIONS: The 'no-show' rate in this population was very low. Measures to reduce this rate (e.g. reducing the waiting list, sending appointment reminders) may be counterproductive as they can discourage successful active problem coping. Additionally, it is doubtful whether if these measures increase the show-rate of less motivated individuals.

Adult↗

Pyridyl-substituted tetrahydrocyclopropa[a]naphthalenes: highly active and selective inhibitors of P450 arom.

The synthesis and biological evaluation of substituted exo-1-(4-pyridyl)-1a,2,3,7b-tetrahydro-1H-cyclopropa[a]naphthalene s as inhibitors of estrogen biosynthesis is described [H (1); 4-OCH3 (2); 5-OCH3 (3); 6-OCH3 (4); 1-CH3, 6-OCH3 (5); 4-OCH3, 7-Br (6); 6-OCH3, 5-Br (7); 4-OH (8); 5-OH (9); 6-OH (10)]. The synthetic key step--the formation of the cyclopropyl ring--was accomplished using the conditions of a modified Wolff-Kishner reduction (N2H5OH/KOH; delta T) and yielded exclusively the exo-configurated diastereomers. The racemic compounds 1-10 showed an inhibition of human placental aromatase (P450 arom) exhibiting relative potencies (rp) from 3.7 to 303 (compounds 8 and 4, respectively; rp of aminoglutethimide (AG) identical to 1, fadrozole = 359). The enantiomers of 4 and 7 were separated by LPLC on tribenzoyl cellulose and by crystallization of the diastereomeric tartrates (4). (1aS,2S,7bS)-(+)-4 (absolute configuration determined by X-ray crystallographic analysis) is the active P450 arom inhibiting enantiomer of 4 and shows a rp value of 617. Compound 4 is a reversible inhibitor showing a competitive type of inhibition and a type II difference spectrum. In vitro 4 influenced other steroidogenic P450 enzymes either not at all (bovine adrenal P450 scc) or only marginally (rat testicular P450 17, bovine adrenal P450 18). In ACTH-stimulated rat adrenal tissue, 4 was less active, inhibiting corticosterone and aldosterone formation compared to AG and fadrozole, respectively. In vivo 4 was not superior to AG as far as the inhibition of the uterotrophic activity of androstenedione (juvenile SD rats) and the reduction of the plasma estradiol concentration (pregnant mares' serum gonadotropin-primed SD rats) are concerned. Compound 4 shows marked antitumor activity in the dimethylbenzanthracene-induced mammary carcinoma of the SD rat: in the postmenopausal model it is at least as active as AG; in the premenopausal experiment it is clearly superior to AG. No induction of hepatic P450 enzymes was observed in the latter experiment. The rp value of 4 toward rat ovarian P450 arom, i.e., 23 (rp of AG identical to 1), is markedly decreased compared to the human enzyme (rp value of 303). From this fact it must be concluded that 4 should be more active in the human than in the rat.

Adrenal Glands↗

Analysis of immunoassays to detect antibodies to hepatitis A virus (anti-HAV) and anti-HAV immunoglobulin M.

Two newly developed anti-HAV tests were assessed, using a total of 1835 sera. These two tests are being distributed under the trademarks Enzymun-Test anti-HAV and Enzymun-Test IgM anti-HAV. The anti-HAV test was compared to anti-HAV tests from other manufacturers and featured a high sensitivity combined with a high level of reproducibility and specificity. In terms of sensitivity, reproducibility and specificity, the IgM test proved to be comparable to other IgM anti-HAV tests used for the diagnosis of acute type A hepatitis. Combining both tests was shown to be useful to recognize an acute or past hepatitis A virus infection. In addition, the high sensitivity of the anti-HAV test makes this test extremely useful to assess the immunoresponse to the hepatitis A vaccine.

Female↗

Aromatase inhibitors. Syntheses and structure-activity studies of novel pyridyl-substituted indanones, indans, and tetralins.

The (E)-2-(4-pyridylmethylene)-1-indanones(E)-1-(E)-5[(E)-1,H;(E)-2,4- OCH3; (E)-3,5-OCH3; (E)-4,4-OH;(E)-5,5-OH] were obtained by aldol condensation of the corresponding 1-indanones with 4-pyridinecarboxaldehyde, and in case of the OH compound (E)-4 subsequent ether cleavage of (E)-2. The synthesis of the (Z)-isomers (Z)-1-(Z)-3[(Z)-1,H;(Z)-2,4-OCH3; (Z)-3,5-OCH3] was accomplished by UV irradiation of the corresponding (E)-isomers. Catalytic hydrogenation of (E)-1-(E)-3 gave the 2-(4-pyridylmethyl)-1-indanones 6-8 (6, H; 7,4-OCH3; 8,5-OCH3). The 2-(4-pyridylmethyl)-substituted indans 11-13 (11,H; 12,4-OCH3; 13,5-OCH3) and the tetralins 16-19 (16,H;17,5-OCH3;18,6-OCH3;19,7-OCH3) were obtained by reduction of the corresponding ketones using N2H4/KOH. The 2-(4-pyridylmethyl)-substituted indanones 9 (4-OH) and 10 (5-OH), indans 14 (4-OH) and 15 (5-OH), and tetralins 20-22 (20,5-OH; 21,6-OH; 22,7-OH) were synthesized by ether cleavage of the corresponding OCH3 compounds. All compounds showed inhibition of human placental aromatase exhibiting relative potencies from 0.9 [(E)-4] to 163 [18; aminoglutethimide (AG) potency identical to 1]. Compounds 13 and 18 showed competitive type of inhibition and a type II difference spectrum, indicating the interaction of the pyridyl-N with the central Fe(III) ion of the cytochrome P450 heme component.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstenedione↗

Diagnosis of human immunodeficiency virus (HIV) infection: multicenter evaluation of a newly developed anti-HIV 1 and 2 enzyme immunoassay.

A new anti-human immunodeficiency virus type 1 and 2 (anti-HIV 1 and 2) test is described. It uses recombinant p24 and peptides covering gp32, gp41, and gp120 to identify HIV-1 and HIV-2 infections. This test has been shown to be specific (99.5%) and sensitive (99.8%). In this respect, the assay was equal or superior to anti-HIV 1 and 2 tests run as references. The test was able to discriminate sera from patients with HIV infections from those from uninfected individuals with excellence; it also exerted high intra- and interassay precisions. The "modular" concept of the test allows the use of single components (gp32 or gp41) to separate between HIV-2 and HIV-1 infections, respectively.

Diagnosis, Differential↗

Boehringer Mannheim modular test concepts in HIV and hepatitis immunoassays.

Anti-HIV-antibody and hepatitis C virus (HCV)-antibody screening tests have to be able to detect a variety of virus antibodies. On the other hand, HIV-antigen specific antibody tests that detect only one kind of antibody are needed for prognosis of disease or for distinguishing infection by different virus subtypes. Usually in an enzyme-linked immunosorbent assay for each individual test an individual solid phase has to be created. For our Boehringer Mannheim Enzymun-Test Diagnostics Assay we used a single universal biotin-binding solid phase in all tests and biotin-labeled specific antigens for the individual tests. The modular system for the antibody tests is a convenient tool for the development of a broad test menu for different viruses. We show that the modular system is suited for screening tests for HIV1, HIV2, or HCV antibodies, as as well as for virus typing or for detection of HIV/p24-specific antibodies in a quantitative assay with high precision.

Antibody Specificity↗

Phosphorylation sites of the nicotinic acetylcholine receptor. A novel site detected in position delta S362.

The delta-subunit of the nicotinic acetylcholine receptor from Torpedo californica electric tissue isolated form receptor purified in the absence of protein phosphatase inhibitors contains a total of four phosphate groups. Three of these are shown to represent phosphoserine groups. The fourth possible represents phosphotyrosine. The phosphate groups are localized within the primary structure: We found phosphoserine in positions delta S361 and delta S377, the predicted sites phosphorylated by PKA and PKC, respectively. In addition, we found that position delta S362 is also phosphorylated. Phosphorylation experiments with the synthetic peptide delta L357-delta K368 show that phosphorylation of this novel site can be catalyzed by PKA and by PKC. It is concluded that the delat-subunit of the acetylcholine receptor is stably and not transiently phosphorylated. Implications for the physiological functions of receptor phosphorylation are discussed.

Animals↗

New aromatase inhibitors. Synthesis and biological activity of pyridyl-substituted tetralone derivatives.

The (E)-2-(4-pyridylmethylene)-1-tetralones 1-7 (1, H; 2, 5-OCH3; 3, 6-OCH3; 4, 7-OCH3; 5, 5-OH; 6, 6-OH; 7, 7-OH) were obtained by aldol condensation of the corresponding 1-tetralones with 4-pyridinecarboxaldehyde, and in the case of the OH compounds 5 and 7 subsequent ether cleavage of the OCH3-substituted 2-(4-pyridylmethylene)-1-tetralones. Catalytic hydrogenation of 1-4 gave the 2-(4-pyridylmethyl)-1-tetralones 8-11 (8, H; 9, 5-OCH3; 10, 6-OCH3; 11, 7-OCH3). Subsequent ether cleavage of 9-11 led to the corresponding OH compounds 12-14 (12, 5-OH; 13, 6-OH; 14, 7-OH). The enantiomers of 11 and 12 were separated semipreparatively by HPLC on triacetylcellulose. All compounds (1-14) showed an inhibition of human placental aromatase exhibiting relative potencies from 2.2 to 213 [compounds 6 and (+)-12, respectively; aromatase inhibitory potency of aminoglutethimide (AG) = 1]. The compounds exhibited no or only a weak inhibition of desmolase [cholesterol side chain cleavage enzyme; maximum activity shown by 12, 23% inhibition (25 microM); AG, 53% inhibition (25 microM)]. In vivo, however, the compounds were not superior to AG as far as the reduction of the plasma estradiol concentration and the mammary carcinoma (MC) inhibiting properties are concerned (PMSG-primed SD rats as well as DMBA-induced MC of the SD rat, pre- and postmenopausal experiments, and the transplantable MXT-MC of the BD2F1 mouse). This is due to a fast decrease of the plasma E2 concentration inhibiting effect as could be shown by a kinetic experiment. In addition, select compounds inhibited rat ovarian aromatase much less than human placental aromatase (12, factor of 10). Estrogenic effects as a cause for the poor in vivo activity of the test compounds could be excluded, since they did not show affinity for the estrogen receptor.

Animals↗

[Pyridyl-substituted tetralone derivatives: a new class of nonsteroidal aromatase inhibitors].

Structural modification of flavone and flavanone, two weak inhibitors of aromatase, led to the new compounds 1-7, the syntheses of which are described as well as the evaluation of their aromatase and desmolase inhibitory potency. With the exception of 2 all compounds show a stronger inhibition of aromatase than the parent compounds and are more effective inhibitors than aminoglutethimide (AG), the only commercially available compound. In contrast to AG compounds 1 and 3-7 exhibit no desmolase inhibitory activity. In case of AG this effect leads to undesirable side effects.

Aromatase Inhibitors↗

[Medical, moral, ethical and legal problems in modern obstetrics].

This paper addresses the problems which have arisen in connection with the improved intensive care of neonates and the possibility of prenatal diagnosis and therapy. Medical problems consist of difficulties in determining the indications. Ethical problems result from the right of decision of the pregnant woman, of her family and of the society beyond the normal physician-patient relationship and there are expert and legal questions, too. A more public evaluation of the patient material may lead to solution of the problems. Ethical and legal principles can be derived from these basic considerations. No new morals and ethics must evolve even if damage to the fetus or malformations can now be recognized antenatally instead of only postnatally as before. Malformations incompatible with life are indications for termination if the pregnant woman so desires. Every other type of malformation is something which the pregnant woman, her family and society must come to terms with. Prenatal medicine is able to soften the consequent burdens for the family and society.

Abortion, Spontaneous↗

[Assessment of peripheral hemodynamics of the fetus using Doppler ultrasound].

Analysis of foetal haemodynamics using Doppler ultrasound is widely applicable in obstetrics in assessing foetal well-being. To evaluate the parameters of foetal circulation we examined 205 pregnant women to ascertain normal velocity ranges of the foetal internal carotid artery and the foetal renal artery. By establishing the ratio between the pulsatility indices of the foetal internal carotid artery, the foetal aorta and the renal artery of the foetus, standards of these were obtained. From this it seems to be possible to gain information on the extent and degree of the centralisation of foetal blood circulation.

Blood Flow Velocity↗

Virus neutralizing and enhancing epitopes characterized by synthetic oligopeptides derived from the feline leukaemia virus glycoprotein sequence.

Synthetic peptides that mimic antigenic determinants of viral proteins were used in vaccine studies of feline leukaemia virus (FeLV) infection. Immunoreactive epitopes on FeLV gp70 and p15E were predicted according to the criteria of their terminal position, hydrophilicity and the probability of them constituting helical structures. Nineteen peptides, consisting of seven to 19 amino acid residues, were synthesized, of which two peptides were derived from the FeLV subtype A, 16 from subtype B and one from subtype C. Rabbits were immunized with individual peptides coupled to keyhole limpet haemocyanin and the specificity and biological activities of these hyperimmune sera were determined by ELISA, Western blotting, virus neutralization and cytotoxicity assays. All sera reacted specifically with the immunizing peptide. Twelve of the 19 peptides induced antibodies against purified gp85 and antibodies to 11 peptides reacted with the whole virus. One peptide representing the carboxy terminus of the transmembrane protein p15E, and two peptides derived from the external glycoprotein gp70 elicited neutralizing antibodies, whereas antisera against four peptides enhanced virus infection in vitro. None of the peptide antisera mediated complement lysis of FeLV-infected cells.

Amino Acid Sequence↗

[Doppler sonography in obstetric diagnosis: I: General physical and clinical principles].

The paper gives an overview of the application in obstetrics of Doppler-ultrasound for blood flow measurements. Both usual methods, the continuous-wave and the pulsed Doppler are compared, including the safety aspects of the investigation. The advantages and disadvantages of quantitative and qualitative analysis of the Doppler spectrum are discussed and the necessary terms as Pulse Repetition Frequency (PRF), High Pass Filter (HPF), sample volume, aliasing and Doppler spectrum explained. The vessels of interest and the clinical importance they reflect are demonstrated. The importance of this new non-invasive mean in the assessment of utero-feto-placental haemodynamics is underlined.

Blood Flow Velocity↗

[Potential clinical application of Doppler ultrasound in obstetrics].

The measurement of fetal and maternal blood flow velocities by Doppler-ultrasound is the first noninvasive method of studying utero-feto-placental haemodynamics. The pulsed Doppler is used by many observers to diagnose variations in the tissue resistance in certain clinical situations. The Doppler-ultrasound get the main importance in cases of intrauterine growth retardation, pregnancy induced hypertension, pregnancies in combination with diabetes mellitus and in cases of intrauterine hypoxia. This paper gives an overview about the clinical range of Doppler-velocimetry-investigations.

Blood Flow Velocity↗