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Biomedical subjects

H Meisel

Publications and source records attributed to H Meisel.

At least 91 records · Page 5Linked to original sources

Heat-induced changes in casein-derived phosphopeptides.

Phosphopeptides derived from casein may function as carriers for calcium and trace elements. In regard to such specific nutritive effects, the heat-induced changes in tryptic phosphopeptides liberated from bovine sodium caseinate as a model system were investigated. Both microwave and oven heating resulted in a marked loss of peptide-bound phosphorous (dephosphorylation) and a decrease of casein-phosphopeptides in the soluble part of the tryptic hydrolysate. It is concluded that hydrolysis of phosphoseryl to seryl residues was the prevailing degradation step to soluble proteolytic products, whereas lysinoalanyl-casein is claimed to be present almost exclusively in the pH 4.6-insoluble part of the tryptic digest.

Animals↗

Comparative inhibition of hepatitis B virus DNA polymerase and cellular DNA polymerases by triphosphates of sugar-modified 5-methyldeoxycytidines and of other nucleoside analogs.

Of a series of 14 nucleoside 5'-triphosphates, those of 2',3'-dideoxy-3'-fluoro-5-methylcytidine, 3'-azido-2',3'-dideoxy-5-methylcytidine, 2',3'-dideoxy-3'-fluoroguanosine, 2',3'-didehydro-2',3'-dideoxy-5-methylcytidine, 2',3'-dideoxy-3'-fluoro-5-ethylcytidine, and 2',3'-dideoxy-3'-fluoroadenosine emerged as the most potent inhibitors of hepatitis B virus DNA polymerase (50% inhibitory dose, 0.03 to 0.35 microM). In contrast, cellular DNA polymerases proved to be resistant to (alpha) or partially affected by (beta) these analogs. These compounds are among the most effective and selective inhibitors of endogenous hepatitis B virus DNA polymerase recognized to date.

Deoxycytidine↗

[Treatment of chronic hepatitis B with interferon alpha-2b].

In a prospective randomized trial 58 patients (46 men, 12 women; mean age 41 [18-65] years) with histologically proven chronic hepatitis B and demonstration of HBs antigen and hepatitis B virus DNA in serum were randomly divided into two groups: 30 patients were treated with recombinant alpha 2b interferon. The interferon was administered subcutaneously, 3 x 10(6) IU, three times weekly for four months. 28 patients served as untreated controls. There was a six-month post-treatment follow-up. Two patients in the treatment group and one in the control group had to be excluded later. In the treatment group one patient responded completely (HBs antigen, HBe antigen and HBV-DNA negative) and eight partially (HBe antigen and HBV-DNA negative). In three patients of the control group, HBe antigen and HBV DNA were no longer demonstrated (P less than 0.05). The loss of HBV features was associated with normalization of serum transaminases activity. Reactivation of liver inflammation after seroconversion was not observed.

Adolescent↗

Inhibition of hepatitis B virus DNA polymerase by 3'-fluorothymidine triphosphate and other modified nucleoside triphosphate analogs.

The 3'-fluoromodified nucleotide analogs 3'-fluorothymidine triphosphate (FdTTP), 2',3'-dideoxy-3'-fluoro-5-chlorouridine triphosphate (F-5CldUTP), 2',3'-dideoxy-3'-fluoro-5-ethyluridine triphosphate (F-5EtdUTP), 2',3'-dideoxy-3'-fluorouridine triphosphate (FdUTP), and 2',3'-dideoxy-3'-fluoro-5-fluorouridine triphosphate (F-5FdUTP) as well as 2',3'-dideoxythymidine triphosphate (ddTTP), 2',3'-didehydro-2',3'-dideoxythymidine triphosphate (ddeTTP), 3'-chlorothymidine triphosphate (CldTTP), and 3'-rhodanothymidine triphosphate (SCNdTTP) were tested for their ability to inhibit hepatitis B virus (HBV)-associated DNA polymerase activity in vitro. The ID50 values of the most potent inhibitors were 0.15 microM for FdTTP, 0.2 microM for ddeTTP, 0.45 microM for ddTTP, and 0.8 microM for F-5CldUTP. SCNdTTP, CldTTP, and F-5EtdUTP were less efficient (ID50 = 3-5 microM), and FdUTP and F-5FdUTP were the least efficient inhibitors (ID50 = 25 microM) of the enzyme activity. Kinetic analysis revealed a competitive type of inhibition for FdTTP and ddeTTP. The Ki values were estimated to be 0.04 microM and 0.08 microM, respectively, compared with a Km value for dTTP of about 0.18 microM.

Dose-Response Relationship, Drug↗

Treatment of chronic hepatitis B with interferon alfa-2b.

A total of 58 patients with histologically confirmed chronic viral hepatitis B and presence of hepatitis B surface antigen and hepatitis B virus DNA (HBV DNA) in the serum were randomized in a prospectively controlled trial. Thirty patients were treated with 3 megaunits of recombinant interferon alfa-2b (INTRON A, R Schering-Plough, Essex Corporation) subcutaneously thrice weekly for 4 months. Twenty-eight controls received no treatment. The post-treatment follow-up period consisted of 6 months. Twenty-eight treated patients and 27 controls completed the protocol. One female patient of the treatment group showed a complete response, and eight other treated patients (32%) showed a partial response to therapy. Three patients in the control group (11%) lost hepatitis B e antigen and HBV DNA spontaneously. This finding is statistically significant (p less than 0.05). The elimination of hepatitis B virus markers from the serum was associated with a normalization of aminotransferase activities in the serum. Reactivation of hepatitis was not observed after seroconversion.

Adult↗

[Treatment of chronic hepatitis B with interferon alpha-2b].

A total of 58 patients with histologically confirmed chronic viral hepatitis B and presence of HBsAg and HBV-DNA in the serum were randomized in a prospectively controlled trial. 30 patients were treated with 3 megaunits of rIFN a-2b s.c. thrice weekly for 4 months. 28 controls received no treatment. The post-treatment follow-up period consisted of 6 months. 28 patients treated and 27 controls completed the protocol. One female patient of the treatment group showed a complete response (loss of HBsAg, HBeAg and HBV-DNA), 8 other patients (32%) revealed a partial response to therapy (loss of HBeAg and HBV-DNA). Three patients of the control-group (11%) lost HBeAg and HBV-DNA spontaneously. This finding is statistically significant (p less than 0.05). The elimination of HBV-markers from the serum was associated with a normalization of aminotransferase activities in the serum. A reactivation of hepatitis was not observed after seroconversion.

Adolescent↗

[The relation of B- and non-A, non-B hepatitis virus--hepatitis B virus (HBV) DNA hybridization studies of the sera in non-A, non-B hepatitis].

Referring to informations of various international groups of investigators who regard the NANBH as HBV-variant the sera of 77 female patients with chronic NANBH and 28 acute phase sera of a NANBH serum bank were tested for HBV-DNA. The sera in question were such ones of a particularly well defined group of patients with unique parenteral source of infections. Though further ALAT attacks were observed, in none of the NANBH-sera HBV-DNA was proved as a sign of an active HBV-replication. This, like the absence of an immunity against the NANBH-virus after HBV-disease and the observed suppression of the HBV-DNA in NANBH-superinfection of HBV-carriers (virus interference), speaks against the hypothesis of a close genetic relationship between the two viruses.

Adult↗

Biologically active peptides in milk proteins.

Bioactive peptides have been identified as digestion products of several food proteins. All the bioactive sequences are hidden in an inactive state inside the polypeptide chain of the larger protein. Milk proteins are a rich source of biologically active peptides such as exorphins (casomorphins), phosphopeptides and immunopeptides. Such peptides are released during intestinal digestion of caseins and whey proteins. They may be involved in regulation of nutrient entry and influence the postprandial metabolism via stimulation of the secretion of hormones. Furthermore, they may exert a stimulating effect on the immune system. These findings offer new aspects for evaluating the nutritive value of food proteins. Moreover, bioactive peptides have already found interesting applications as dietary supplements and as pharmaceutical preparations.

Amino Acid Sequence↗

Chemical characterization of bioactive peptides from in vivo digests of casein.

The in vivo formation of biologically active caseinopeptides was studied. It was proved that bioactive peptides were released in the small intestine of minipigs in the course of luminal digestion of diets containing bovine casein. An opioid peptide and a phosphopeptide were isolated from jejunal chyme and were chemically characterized. The opioid peptide has been identified as a fragment of beta-casein (60-70). This peptide, named beta-casomorphin-11, displayed substantial opioid activity in an opiate receptor-binding assay. The caseinophosphopeptide has been shown to be a fragment of alpha s1-casein (66-74). Casein-derived phosphopeptides exhibit a potent ability to form soluble complexes with Ca and trace elements. Evidence exists that casomorphins and caseinophosphopeptides participate in the regulation of nutrient entry.

Animals↗

[Hepatitis B screening in pregnant patients and their children. A Greifswald perinatology-pediatric study. II. Pediatric findings].

Hepatitis B virus carriers were identified by a systematic screening of women during the last trimester of pregnancy. With 0.5% the HBV carrier incidence was found to be constant over years. 25 children of HBsAg positive women were followed after 2-4 years in order to define the risk of vertical transmission. One infant died due to the sequelae of a congenital malformation. In 12 of the remaining infants HBV markers were found after different intervals, in 10 of them also clinical and paraclinical symptoms of HBV infection could be diagnosed. The results are discussed in relation to the maternal serologic status and with regard to different preventive measures. Summarizing our results the following recommendations can be given: A mass screening for HBV during pregnancy is the only safe method of diagnosing HBsAg positive carriers. All newborns of HBsAg positive pregnants should be vaccinated immediately after birth, both actively and passively.

Carrier State↗

Chemical characterization of a caseinophosphopeptide isolated from in vivo digests of a casein diet.

The in vivo formation of phosphopeptides derived from bovine casein was proved in small intestinal chyme of minipigs after ingestion of a diet containing casein. The main phosphopeptide was identified as a fragment of alpha s1-casein (f 66-74): SerP-SerP-SerP-Glu-Glu-Ile-Val-Pro-Asn. It is discussed, that caseinophosphopeptides are likely to promote the intestinal absorption of calcium and trace elements.

Amino Acids↗

Chemical characterization and opioid activity of an exorphin isolated from in vivo digests of casein.

The in vivo formation of an opioid peptide (exorphin) derived from beta-casein has been proved for the first time. It was isolated from duodenal chyme of minipigs after feeding with the milk protein casein. The exorphin has been identified as a beta-casein fragment by end-group determinations and qualitative amino acid analysis of the purified peptide. This peptide, named beta-casomorphin-11, displayed substantial opioid activity in an opiate receptor-binding assay.

Amino Acids↗

[Hepatitis and imported infectious diseases. A. Hepatitis. 1. Virologic findings in acute hepatitis].

The properties of the hepatitis-A-virus and the hepatitis-B-virus are described. The authors refer to the fact that despite the far-reaching development, particularly in the field of the hepatitis-B-infection up to a usable active immunoprophylaxis many questions concerning the natural history, pathogenesis and epidemiology are still unclarified. The development of demonstration methods of the 3rd generation and their use in the diagnostics of hepatitis rendered possible the gain of new realizations. The authors contributed to the introduction of these methods essentially by own developments, as for instance of ELISA for the demonstration of HBeAg and anti-HBe. The solution of some still open questions can be expected only by the successful establishment of a suitable virus-host-cell system.

Acute Disease↗

Comparison of direct and indirect two-site binding enzyme immunoassay.

Rabbit IgG, directed against HBsAg, was purified by positive and by negative affinity chromatography and applied in horseradish peroxidase labelled as well as in unlabelled form in the direct and indirect two-site binding enzyme immunoassay (EIA). Comparing direct and indirect assay the latter is more sensitive and less conjugate consuming. In contrast to the indirect assay in which antibodies, purified by positive affinity chromatography, do not alter detection limit, a 4- to 8-fold higher sensitivity was achieved in the direct EIA in contrast to antibodies, purified by negative affinity chromatography. In the indirect EIA unlabelled second and labelled third antibodies were incubated successively as well as simultaneously. The latter procedure shortened the assay time but needed antibodies purified by positive affinity chromatography and a 10-fold higher conjugate concentration. Greatest sensitivity was obtained in the indirect EIA by the use of labelled second and labelled third antibodies (20-30 ng/l HBsAg).

Chromatography, Affinity↗

[Risk of hepatitis B in endoscopy personnel].

By anamnestic inquiry and investigation for HBsAg and anti-HBs (RIA) of 120 staff members from 18 endoscopic centers, we found reference to remarkable spread of hepatitis B. Its incidence in endoscopic staff is unambiguously higher than in personal of internal wards. So, 8.3 per cent of endoscopic workers were positive for HBsAg, and anti-HBs was found in 29.7 per cent of them. This study accentuates the high danger by gastro-enterologic patients, who not rarely are HBsAg-positive and infectious. Preventive measures are recommended.

Endoscopy↗