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Biomedical subjects

J Kühn

Publications and source records attributed to J Kühn.

17 recordsLinked to original sources

N-Terminal pyrazinones: a new class of peptide-bound advanced glycation end-products.

The reaction of peptide Gly-Ala-Phe with the alpha-dicarbonyl compounds glyoxal and methylglyoxal was studied under physiological conditions (pH=7.4, 37 degrees C). Using HPLC with UV and fluorescence detection, a rapid derivatization of the peptide and the concomitant formation of well-defined products were observed. The products, which showed characteristic UV absorbance (lambda(max)=320 to 340 nm) and fluorescence (lambda(ex)=330 to 340 nm, lambda(em)=395 to 405 nm), were identified by ESI-MS and NMR spectroscopic analysis as the N-terminally pyrazinone-modified peptides I (N-[2-(2-oxo-2H-pyrazin-1-yl)-propyl]-phenylalanine) and II (N-[2-(5-methyl-2-oxo-2H-pyrazin-1-yl)-propionyl]-phenylalanine). Model experiments revealed that the reactivity of the N-termini of peptides towards a derivatization by glyoxal is in the same order of magnitude as that of arginine, which generally is attributed as main target for alpha-dicarbonyl compounds in proteins. Incubation of insulin with glyoxal proved the protein-bound formation of pyrazinones, with the N-terminus of the B-chain as the main target. According to these results, we conclude that N-terminal pyrazinones represent a new type of advanced glycation end-products (AGEs) with significance for biological systems and foods.

Animals↗

[Ecthyma contagiosum (Orf) as an uncommon differential diagnosis of infections of the hand].

Orf of the hand is considered as an uncommon viral infection which is usually acquired through contact with infected sheep and goats. Indirect infections through contaminated knives or meat have been reported. Many authors feel that the disorder is more common than reported because the disease is often misdiagnosed and the course is usually self-limiting with spontaneous healing within several weeks. Diagnosis is mainly made by patient's history and clinical course. It is important to know the benign nature of human orf, since complications seem to be caused by overtreatment.

Biopsy↗

[Vena cava filter--prevention of pulmonary embolism. Report of clinical experiences].

Between 1982 and 1997 inferior vena cava filters were implanted in 182 patients. Indications were recurrent pulmonary embolism, massive embolism and prophylactic use prior to planned high-risk-operations upon patients with thromboembolic complications in shorter history. Kimray-Greenfield, Cardial and Vascor-systems were implanted. Mortality was 0, neither relevant bleedings, nor infections occurred. Vena-cava-filters prevented from re-embolism in 98%. During hospitalisation 3 cases of re-embolism (1.6%) were noticed due to incorrect filter-placement. One patient died (< 1%). Follow-up-examinations were performed in 74 cases 6 to 24 months after implantation. We discovered 8 cases (11%) of filter-migration, 3 cases (4%) of filter-kinking, one case of filter-perforation and one case of filter-shrut-fracture. All these patients remained without clinical sequelae. Cava-thrombosis was found in 2 patients 6 to 24 months after filter-insertion (2.7%). There was no sign of re-embolism in our longterm follow-up. In our opinion the vena cava filter is an effective and safe method to prevent pulmonary re-embolism. Handling is quite easy and filter complications are low. In some elected cases prophylactic use of vena cava filters in high-risk-patients may be indicated.

Adult↗

Detection of HIV in human vitreous.

Assay of human vitreous specimens obtained postmortem for HIV antibodies, or HIV p24 antigen, is reported to be a reliable technique to demonstrate HIV infection in possible cornea donors from whom serum could not be obtained. We tested three vitreous samples obtained during vitrectomy from two HIV-positive patients. One patient exhibited the clinical AIDS syndrome. HIV antigen and antibody tests were negative in all specimens. HIV proviral DNA was detected by PCR only in the vitreous of the patient with AIDS. Therefore, testing only vitreous samples is insufficient to exclude HIV infection in potential cornea donors.

Adult↗

Effect of propranolol and disopyramide on left ventricular function at rest and during exercise in hypertrophic cardiomyopathy.

In 19 patients with hypertrophic cardiomyopathy (15 males, 4 females, mean age 49.2 +/- 10.8 years) left ventricular function was studied with radionuclide ventriculography at rest and during exercise in a crossover design without intervention and after disopyramide and propranolol treatment. 15 of the 19 patients had a resting or latent intraventricular gradient of more than 30 mm Hg. Left ventricular function at rest and during exercise was evaluated before medication, 90 min after oral administration of 200 mg disopyramide or 160 mg propranolol and after 3 weeks of oral therapy with disopyramide 200 mg 2 times a day or propranolol 80 mg 4 times a day. After long-term treatment with disopyramide, resting ejection fraction decreased from 72 +/- 12 to 69 +/- 14% (p less than 0.01) and peak ejection rate (PER) decreased from 3.46 +/- 135 to 3.24 +/- 65 end-diastolic volume (EDV).s-1 (p less than 0.01). Peak filling rate (PFR) at rest decreased from 3.01 +/- 0.8 to 2.77 +/- 0.63 EDV.s-1 (p less than 0.05). Time to peak filling rate (TPFR) at rest and during exercise after acute and chronic therapy did not change compared to control values. Acute and long-term administration of propranolol lead to a significant reduction in heart rate at rest and during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

[Comparison of 4 crossmatching methods for predicting the success of platelet transfusion].

Long term platelet transfusion support often results in alloimmunization of the recipients and refractoriness to further platelet transfusions. Crossmatch tests between the recipients' serum and the donor platelets offer a potential solution to this problem. In the present study, 207 donor-recipient pairs were studied in 65 patients. We compared four assays (LCT, PAIFT, ELISA and MAIPA) in their ability to predict the response in patients receiving multiple platelet transfusions. All four techniques showed a similar predictability of transfusion outcome (79-80%). Of the four assays, the LCT had the highest specificity (100%) and the PAIFT had the highest sensitivity (70%). In comparison to the three other techniques, the MAIPA assay, a glycoproteinspecific immunoassay, offers the possibility to distinguish between HLA-specific (cytotoxic and noncytotoxic) and platelet-specific antibodies in the same serum specimens. Our results demonstrate that HLA antibodies are the major cause of platelet transfusion refractoriness. Platelet specific (i.e. anti-Zwb) and ABO antibodies are involved in approximately 10%.

Adolescent↗

Frequent detection of antibodies to hepatitis B virus x-protein in acute, chronic and resolved infections.

Recombinant MS2- or beta gal fusion proteins containing parts of hepatitis B virus (HBV) HBx-, HBc-, and HBs-amino acid sequences were expressed in Escherichia coli and were used to screen 96 and 60 serum samples of HBV infected and uninfected patients, respectively, for the corresponding antibodies by immunoblotting. Antibodies against HBx were detected in 20 out of 65 sera of patients with previous resolved HBV-infection, in 3 out of 7 patients with persistent infection, and in 9 out of 24 sera of patients with acute HBV infection. The specificity of the immune reaction was confirmed by competition experiments with MS2- and beta gal-HBx fusion proteins, and by the lack of HBx antibodies in the sera of uninfected patients. Hbs and HBc antibodies were detected less frequently by immunoblotting with recombinant fusion proteins than by a commercial immunoassay. Our results indicate that HBx antibodies are induced early and frequently during HBV infection suggesting that the HBx protein is an early antigenic protein expressed in vivo.

Cloning, Molecular↗

Homology of the HSV-2 "a-sequence" to cellular sequences.

Bgl-II fragments of the genome of Herpes simplex virus type 2 (HSV-2) HG-52 were cloned into the vector p-Neo and were used to screen the complete HSV-2 genome for regions cross-hybridizing with the genome of HEL cells. Most extensive cross-hybridizing activity was observed with a 530 bp SstII subfragment of the viral BamHI G DNA-fragment (contained in Bgl II F), which spans the joint and the viral a-sequence. From a lambda-L47 library, a cellular 15 kb HindIII DNA fragment was subcloned in pBR 322 which contained a 1920 bp SstII subfragment having strong cross-hybridizing activity with the 530 bp Sst II fragment of HSV-2 BamHI G. Within this 1920 bp Sst II fragment the cross-hybridizing activity was confined to a 230 bp Bgl I/Hpa II subfragment. This 230 bp fragment (including the flanking sequences) was analyzed in comparison to the viral a-sequence. Sequence data revealed a (G + C) content of 66% in the cellular and 81% in the viral DNA fragment, which is mainly determined by an extremely (G + C) rich 16-fold direct repeat (DR2) at the 5'-end. The homology between both DNA-fragments varies between 56% and 79% within the L-S inversion region. Both sequences, furthermore, show homology to the human c-myc protooncogene.

Animals↗

[Comments on so-called "chronic" and "therapy refractory" depression].

The problems of so-called "therapy resistant or chronic" depression has been investigated on own patients of the year 1986, but simply one chronic example could be noticed. Configurations-frequence-analytic research didn't essentially result in significant statements. It is referred to that the frequent occurrence of the so-called "therapy resistant" depressions described by some authors, could be in connection with limited diagnosis inventories and insufficient to the personality orientated therapy regime.

Adult↗

Human cytomegalovirus replicates in primary human bone marrow cells.

As an attempt to elucidate further the pathogenesis of human cytomegalovirus (HCMV) infection the replication of HCMV in primary human bone marrow cells (BMC) has been investigated. It was found that BMC held in culture in general were susceptible to HCMV infection. Compared to human embryonic lung cells, however, the replicative cycle of HCMV AD169 in BMC as determined by the analysis of viral protein and DNA synthesis was delayed and productive virus infection was restricted to a subset of BMC not exceeding 21% of the total cell population. Both of these phenomena may explain the short-term persistence of HCMV in BMC cultures which was observed over 3 months. By experiments with specifically enriched and depleted cell populations and by indirect double immunofluorescence experiments we found that both bone marrow fibroblasts and a subset of bone marrow stem cells supported productive virus infection. The finding that HCMV replicates in early stem cells of the human bone marrow may explain important aspects of the pathogenesis of HCMV infection including the presence of HCMV in peripheral blood leukocytes.

Bone Marrow↗

[Laboratory methods for adenoviruses. XI. Determination of hexon and antihexon-IgA in conjunctival secretions using ELISA].

The possibility of a rapid diagnosis of adenovirus conjunctivitis was studied by demonstrating genus-specific adenovirus hexon antigen or antihexon IgA antibodies in conjunctival secretions by an ELISA. Hexon was found in 44% of about 100 patients with adenovirus conjunctivitis, proven by virus isolation, antihexon in 53%, either one or both in 69% of the conjunctival swabs from the acute phase. Hexon was found in the acute phase more frequently, antihexon in the convalescent phase. In patients with conjunctivitis of different etiology no hexon was found, whereas antihexon IgA was found in a few cases.

Adenoviridae Infections↗

Isolation and identification of enteric adenoviruses.

Thirty-four out of 64 faecal samples with adenovirus particles, as seen by electron microscopy, were found to contain adenovirus 40 or 41 by direct isolation and neutralization in Chang's conjunctival cells, mostly within one week. (Ad40 and 41 candidate viruses are serologically related.) 6 other adenovirus species were isolated; 6 samples gave equivocal results, and 18 were negative. A genus-specific ELISA with an antihexon coat yielded positive results in 40 out of 55 samples; the test failed to identify adenovirus antigen in 10 out of 17 specimens, which were found negative by culture. All of them were negative by immunfluorescence of inoculated Chang cell cultures. Hence the failures are probably due to insufficient amount of virus in the samples. The predominance of only two adenovirus species associated with gastroenteritis in children and the ease of cultivating and identifying them should help to elucidate their etiological significance.

Adenoviridae Infections↗