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Biomedical subjects

F Hofmann

Publications and source records attributed to F Hofmann.

413 records · Page 23Linked to original sources
PubMedDate not supplied

Enhanced chemiluminescent immunoassay for aldosterone.

A solid phase immunoassay for aldosterone using enhanced chemiluminescent detection has been developed. Monoclonal antibodies against aldosterone were used for the immune reaction and compared with polyclonal antibodies. Uniform Protein A coated polystyrene tubes were used as solid phase for the monoclonal antibody and second (anti-rabbit) antibody coated tubes for the polyclonal antibody. Horseradish peroxidase was covalently linked to aldosterone as enzyme label. Optimum conditions were established for the generation and measurement of the luminescent reactions using luminol, p-iodophenol as enhancer and hydrogen peroxide. The advantages of this assay are the high sensitivity with a detection limit of 100 fg/tube, the prolonged luminescence signal with a simplification of the measurement (simpler detectors, external start pipetting) and the short measure time with the possibility of repeated measurement. The coefficients of variation were 4.2%-7.3% in the concentration range 140-1180 pmol/l. The assay showed a significant correlation (r = 0.91) with the ELISA. The aldosterone concentrations in plasma and saliva of patients with Conn's syndrome were significantly increased, and in patients with Addison's disease were found near the detection limit.

Aldosterone↗
PubMedDate not supplied

Inhibitors of protein kinases: CGP 41251, a protein kinase inhibitor with potential as an anticancer agent.

CGP 41251 was originally identified as an inhibitor of protein kinase C (PKC), inhibiting mainly the conventional PKC subtypes, and subsequently shown to inhibit the vascular endothelial growth factor (VEGF) receptor kinase insert domain-containing receptor, which is involved in angiogenesis. CGP 41251 inhibits reversibly intracellular PKC activity, induction of c-fos and the corresponding activation of the mitogen-activated protein kinase induced by either tumor promoting phorbol esters, platelet-derived growth factor, or basic fibroblast growth factor, but not by the epidermal growth factor. CGP 41251 inhibited the ligand-induced autophosphorylation of the receptors for platelet-derived growth factor, stem cell factor, and VEGF (kinase insert domain-containing receptor) that correlated with the inhibition of the mitogen-activated protein kinase activation, but did not affect the ligand-induced autophosphorylation of the receptors for insulin, insulin-like growth factor-I, or epidermal growth factor. CGP 41251 showed broad antiproliferative activity against various tumor and normal cell lines in vitro, and is able to reverse the p-glycoprotein-mediated multidrug resistance of tumor cells in vitro. CGP 41251 showed in vivo antitumor activity as single agent and inhibited angiogenesis in vivo. Thus, CGP 41251 may suppress tumor growth by inhibiting tumor angiogenesis (via its effects on the VEGF receptor tyrosine kinases) in addition to directly inhibiting tumor cell proliferation (via its effects on PKCs).

Antineoplastic Agents↗
PubMedDate not supplied

Purified dihydropyridine-binding site from skeletal muscle t-tubules is a functional calcium channel.

Many excitable cells contain at least two different voltage-dependent Ca channels (L- and T-type). The cardiac, slow, L-type Ca channel is further modulated by cyclic AMP-dependent phosphorylation, which increases the probability of it being open, and is readily blocked by Ca channel blockers including dihydropyridines and phenylalkylamines. The tritiated congeners of these blockers bind in vitro to sites which have the same pharmacological characteristics as those observed in vivo, that is, stereospecific and allosteric interaction between distinct sites. The dihydropyridine-binding site purified from skeletal muscle t-tubules contains three peptides of relative molecular mass (Mr) 142,000 (142K), 56K and 31K. The cAMP kinase incorporates one mol phosphate per mol of the 142K peptide and binding of (+)PN-200/110, a potent Ca antagonist, is allosterically affected by D-cis-diltiazem and verapamil. The purified dihydropyridine-receptor complex has also been incorporated into phospholipid bilayer membranes. Here, we show for the first time that the complex can be reconstituted to form a functional 20-pS Ca channel that retains the principal regulatory, biochemical and pharmacological properties of membrane-bound L-type Ca channels.

Allosteric Regulation↗
PubMedDate not supplied

Differential distribution of four hyperpolarization-activated cation channels in mouse brain.

Hyperpolarization-activated cation currents, termed I(h), are observed in a variety of neurons. Four members of a gene family encoding hyperpolarization-activated cyclic-nucleotide-gated cation channels (HCN1-4) have been cloned. The regional expression and cellular localization of the four HCN channel types in mouse brain was investigated using in situ hybridization. The expression of HCN1 was restricted to the olfactory bulb, cerebral cortex, hippocampus, superior colliculus and cerebellum. In contrast, HCN2 transcripts were found at high levels nearly ubiquitously in the brain, and the strongest signals were seen in the olfactory bulb, hippocampus, thalamus and brain stem. HCN3 was uniformly expressed at very low levels throughout the brain. Finally, HCN4 transcripts were prominently expressed selectively in the thalamus and olfactory bulb. Some neurons expressed two or more HCN channel transcripts including hippocampal pyramidal neurons (HCN1, HCN2 and low levels of HCN 4) and thalamic relay neurons (HCN2 and HCN4). Our results demonstrate that each HCN channel transcript has a unique distribution in the brain. Furthermore, they suggest that the heterogeneity of neuronal I(h) may be, at least in part, due to the differential expression of HCN channel genes.

Amino Acid Sequence↗
PubMedDate not supplied

A cGMP kinase mutant with increased sensitivity to the protein kinase inhibitor peptide PKI(5-24).

Synthetic peptides corresponding to the active domain of the heat-stable inhibitor protein PKI are very potent inhibitors of cAMP-dependent protein kinase, but are extremely weak inhibitors of cGMP-dependent protein kinase. In this study, we tried to confer PKI sensitivity to cGMP kinase by site-directed mutagenesis. The molecular requirements for high affinity inhibition by PKI were deduced from the crystal structure of the cAMP kinase/PKI complex. A prominent site of interaction are residues Tyr235 and Phe239 in the catalytic subunit, which from a sandwich-like structure with Phe10 of the PKI(5-24) peptide. To increase the sensitivity for PKI, the cGMP kinase codons at the corresponding sites, Ser555 and Ser559, were changed to Tyr and Phe. The mutant cGMP kinase was stimulated half maximally by cGMP at 3-fold higher concentrations (240 nM) than the wild type (77 nM). Wild type and mutant cGMP kinase did not differ significantly in their Km and Vmax for three different substrate peptides. The PKI(5-24) peptide inhibited phosphotransferase activity of the mutant cGMP kinase with higher potency than that of wild type, with Ki values of 42 +/- .3 microM and 160 +/- .7 microM, respectively. The increased affinity of the mutant cGMP kinase was specific for the PKI(5-24) peptide. Mutation of the essential Phe10 in the PKI(5-24) sequence to an Ala yielded a peptide that inhibited mutant and wild type cGMP kinase with similar potency, with Ki values of 160 +/- 11 and 169 +/- 27 microM, respectively. These results suggest that the mutations Ser555Tyr and Ser559Phe are required, but not sufficient, for high affinity inhibition of cGMP kinase by PKI.

Amino Acid Sequence↗
PubMedDate not supplied

Does the concurrent administration of an inactivated hepatitis A vaccine influence the immune response to other travelers vaccines?

BACKGROUND: Travelers seeking protection from hepatitis A also often need protection against other infections, prevalent at their destinations. METHODS: A total of 396 volunteers received not only a hepatitis A vaccine but also either a vaccine against polio, hepatitis B, diphtheria, tetanus, yellow fever, Japanese encephalitis, typhoid fever or rabies according to their individual needs. We investigated the potential influence of the hepatitis A vaccination on the immune response to the other travelers vaccines that were administered concurrently. RESULTS: With seroprotection rates of 100% for yellow fever, Japanese encephalitis and rabies immunization and tetanus boosters our data demonstrate that the concurrent administration of hepatitis A vaccine does not compromise the immune response of these vaccines. Also for oral typhoid, hepatitis B and diphtheria vaccination we did not detect a negative influence of concurrent hepatitis A vaccine administration as compared with respective vaccinations when given alone. Prior to vaccination, more than one third of our subjects lacked protective antibody levels against diphtheria and only 44% of initially seronegative travelers seroconverted to an anti-diphtheria titer > or = 0.01 mIU/mL, supporting a need for an additional dose. Furthermore, only two thirds of the vaccinees tested prior to vaccination were protected against polio type 3, and the seroconversion rate following the administration of oral polio vaccine, was lower for viral type 3 (80%), as has been previously demonstrated in settings without concurrent other vaccinations. CONCLUSION: No negative effect of concurrent travelers vaccinations on the immune response of a hepatitis A vaccine has been detected in a previous report, and, likewise our data suggest no impairment of the antibody response of these travelers vaccines by the concurrent administration of the hepatitis A vaccine.

Adolescent↗
PubMedDate not supplied

[Surgical gloves--how well do the protect against infections?].

Health care workers (HCW) in surgery are at high risk for bloodborne infections (BBI) e.g. by hepatitis-B(HB)-, hepatitis-C(HC)- and HI-virus. On the other hand, infectious medical staff can cause nosocomial BBI in patients, too. Intact gloves provide an efficient barrier against BBI but glove perforations are common during several surgical procedures. A review of studies on glove perforations during different surgical operations was carried out with special regard to user, number and location of perforations, duration and kind of operation. We compared the results with the frequency of glove perforation during operations in 1938 single used gloves. They were collected after different surgical procedures in a department for general surgery and tested for perforation by 1-liter-water-filling method according to DIN 455/1. The product used during the period of this investigation was Sempermed sterile latex surgical glove. Most perforations were found on the index finger and thumb of the non-dominant hand. Duration of operation, role of the user (primary surgeon) and kind of operation are predictors for the incidence of glove perforations. Double gloving, endoscopic and no-touch techniques decrease the possibility of blood contact during operation. Indicator systems are useful for detection of the loss of glove integrity. Due to the high perforation rate found in this study glove change as a routine during surgical procedures should be discussed (e.g. every 30 minutes).

Blood-Borne Pathogens↗
PubMedDate not supplied

[Not Available].

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Brazil↗
PubMedDate not supplied

[Not Available].

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Cardiology↗
PubMedDate not supplied

[Prenatal rubella diagnosis].

Primary rubella infections during the first trimester of pregnancy are an indication for the termination, although not all of fetuses will be infected. Concerning this situation a prenatal rubella diagnostic in 55 pregnant women was carried out to demonstrate a fetal infection. Simultaneously or separately, as methods the determination of rubella IgM antibodies in fetal blood, the demonstration of viral RNA by DNA-RNA-hybridization and the cultivation of rubella virus from amniotic fluid samples were used. In 7 of 40 women the investigation of amniotic fluids showed a positive reaction of the hybridization, in 2 cases a rubella virus could be isolated. IgM rubella antibodies were found in 5 fetuses. Because of its insufficient effectivity at present the prenatal rubella diagnostic should be applied only in special situations, e.g. in cases of a wanted child.

Amniotic Fluid↗
PubMedDate not supplied

[Mumps--occupational exposure and aspects of epidemiologic susceptibility].

1041 persons working in the university hospital of Freiburg, Germany, were tested for mumps antibodies. The first part of the investigation was conducted between 1986 and 1988, the second one in 1992. Significant decrease in seroprevalence between study I (67% immune) and study II (63% immune) was found. Average immunity of paediatric nurses was significantly higher (76%) than that of non-exposed persons (59.7%). 195 persons were vaccinated (live vaccine) and 84.6% seroconverted.

Adolescent↗
PubMedDate not supplied

[Efficacy of hepatitis B preventive vaccination].

Health care workers are at increased hepatitis B risk. In the course of a study with 5035 persons occupied at the Freiburg university hospital, efficacy of hepatitis B vaccination and duration of protection were investigated. Estimations of post-vaccination-anti Hbs showed that women, younger persons, persons with a body mass index < 25 and non-smokers had higher anti Hbs concentrations than men, elderly persons overweight persons and smokers. 2% of female and 1.5% of male vaccinees did not develop anti Hbs and 4.8% and 7.1%, respectively were low responders (anti Hbs < 100 < 10 IU/l). Estimations of vaccination efficacy revealed that even 10 years after basic immunisation at least 50% of all vaccinees should have anti Hbs concentrations > 100 IU/l. The results of the study show that vaccination of children in accordance with German and WHO recommendations will afford full protection (anti Hbs > 10 IU/l) in at least 99% of all cases.

Adult↗