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Biomedical subjects

F Herbst

Publications and source records attributed to F Herbst.

At least 91 records · Page 5Linked to original sources

Phosphorylation and dephosphorylation of the natriuretic peptide urodilatin (CDD-/ANP-95-126) and the effect on biological activity.

Urodilatin (CDD-/ANP-95-126), a new peptide hormone from human urine, is comprised of the same amino acid sequence as cardiodilatin (CDD-99-126/alpha-hANP) except for N-terminal extention by four amino acid residues. The presence of the recognition sequence Arg101-Arg-Ser-Ser104 for the cyclic AMP-dependent protein kinase enables rapid phosphorylation in the Ser104-position. Phosphorylation of urodilatin is associated with decreased vasorelaxant potency, while dephosphorylation of "phospho-urodilatin" by acidic phosphatase completely restores bioactivity.

Acid Phosphatase↗

Degradation of porcine brain natriuretic peptide (pBNP-26) by endoprotease-24.11 from kidney cortical membranes.

Porcine brain natriuretic peptide of 26 amino acid residues (pBNP-26) is inactivated by endoprotease-24.11 (EC 3.4.24.11) of kidney cortical membranes. In contrast to human alpha atrial natriuretic peptide/cardiodilatin (ANP/CDD) showing a single major cleavage within the disulfide-linked loop between Cys and Phe in position 7 and 8, pBNP-26 is cleaved at several sites. Although both pBNP-26 and ANP/CDD exhibit Cys-Phe peptide bonds at the corresponding positions this bond is not cleaved in BNP-26.

Amino Acid Sequence↗

The heart is the center of a new endocrine, paracrine, and neuroendocrine system.

This review indicates that the heart is a polypeptide-producing organ which should be classified among the traditional endocrine tissues. Cardiac hormones have only been known for a few years, the discovery of their endocrine functions, however, occurred in the 1950ies when Gauer, Henry and Kisch observed specific physiological and morphological features of the heart atria indicative of an endocrine activity. Because of their basic effects many target organs involved in the regulation of body fluid pressure and composition are related to this endocrine organ located in the atrial appendages of the heart. The compact endocrine portion of the heart is built up by myoendocrine cells which form the functional endocrine units and produce a variety of polypeptide hormones called cardiodilatin (CDD) or atrial natriuretic polypeptide (ANP), which belong to one family. Also, co-storage of a partially homologous regulatory polypeptide called brain natriuretic polypeptide (BNP) occurs, as has been determined by immunohistochemistry and radioimmunoassay. CDD and/or BNP are found in numerous organs where they exert paracrine and neurocrine functions, e.g., in the brain, peripheral nervous system, kidney, and adrenal medulla. In these organs, a differential post-translational processing of cardiac polypeptides is observed, resulting in different functional activities according to discriminating receptor interactions and degrading metabolism. Some of the extra-auricular sites of synthesis and storage of CDD-like peptides are briefly mentioned. In summary the heart constitutes the center of a multilocal and multifunctional system of specific cardiac polypeptides of endocrine, paraneuronal, and neuronal character.

Animals↗

The prognostic value of plasmaproteins in patients with abdominal sepsis.

In the course of the history of patients with severe peritonitis, opsonins, complements and other proteins of the plasma showed no significant difference between the data of the patients who later died or survived. We conclude that simple parameters like platelet count, creatinine and respiratory function are more sufficient.

Adult↗

Isolation and structural analysis of "urodilatin", a new peptide of the cardiodilatin-(ANP)-family, extracted from human urine.

Two major forms of cardiac peptides have been established in the last few years: (a) a prohormone of 126 amino acids (CDD/ANP-1-126) in the endocrine heart and (b) the circulating CDD/ANP-99-126 (= alpha ANP) in blood plasma. The method we applied earlier to isolate the circulating form of cardiodilatin from human blood was used to detect and analyze the biologically active, predominant form of the same polypeptide family excreted by the kidneys. Each step of the isolation procedure was followed up by a bioassay using an in vitro vascular smooth muscle relaxation test and a highly specific RIA against cardiodilatin (CDD-99-126) for the initial purification steps. The polypeptides excreted in 1000 l of normal human urine were adsorbed to 2.5 kg of alginic acid, and after elution and lyophilization processed on a G-25 Sephadex column. The obtained crude polypeptide fractions were applied to ion-exchange chromatography. Thereafter four steps of HPLC were carried out to purify the polypeptide which was the suggested form of cardiodilatin (CDD) in human urine. The amino acid analysis and gas phase sequence analysis showed that the main form of urinary cardiodilatin is a 32 amino acid residue containing molecule, cardiodilatin-95-126. The molecule is N-terminally extended compared to the circulating CDD-99-126. This suggests that the analyzed urinary peptide is not the residual plasma form, filtrated and renally cleared from blood, but probably a polypeptide produced and processed in the kidney tubules and cleaved by a different postranslational process. Therefore, this vasorelaxant polypeptide is called urodilatin.

Amino Acid Sequence↗

[Local recurrence after colorectal cancer].

A prospective study was undertaken of the incidence, symptoms, diagnostic measures and therapy of local recurrence of colorectal carcinoma following radical surgical management. 156 (22%) out of 715 patients developed recurrence of the tumour, which was local in 90 patients. In addition, 36 patients with LR from other hospitals were treated. Half of the patients were symptom free at the time of diagnosis. 109 out of the 126 patients were treated by surgery, a radical operation being feasible in 53 cases. 50% of these have survived for at least 17 months, 30% for 36 months. The operative mortality was low (4.6%), although extensive surgery was necessary in most of the cases. The results of this study support the hypothesis that a postoperative follow-up programme for patients with colorectal cancer leads to early detection of local recurrence and improves the chance of cure by surgical treatment.

Aged↗

Results of a rigorous follow-up system in colorectal cancer.

Results of a computer-aided follow-up programme for patients with colorectal cancer are analyzed. Between 1978 and 1987 1293 patients underwent this programme, the drop-out rate was 17%. 299 recurrences in 168 patients were discovered (40% local recurrence, 29% liver metastases and 31% others). Fifty-one per cent of patients with local recurrence and 47% with liver metastases were symptom free. Radical surgery could be performed in 50% of local recurrences and in 26% of liver metastases. The three year survival rate after radical surgery for recurrence was 35% for local recurrences and 33% for liver metastases, the five-year-survival rate 23% and 15%, respectively.

Cohort Studies↗

Primary hepatic cancer--the role of limited resection and total hepatectomy with orthotopic liver replacement.

Between 1977 and 1986, 172 patients with primary hepatic cancer were treated at the Department of Surgery I, University of Vienna Medical School. In 76 cases (80%) males, 20% females), cirrhosis of the liver was also present. Ninety patients underwent curative surgery (hepatic resection in 64, and liver transplantation in 26 cases). There were no early tumor stages. Forty-five large tumors were confined to one lobe, 42 involved both lobes, 3 even invaded adjacent structures, the majority (74%) being hepatocellular carcinomas. Forty-four of the 64 liver resections were performed in patients with otherwise normal livers (mortality 18%), while 20 patients had associated liver cirrhosis. In view of the extremely high mortality rates after extended liver resection, only limited local resections have been performed in cirrhotic malignancies since 1982 (mortality 25%). Perioperative mortality (25% overall) was due mainly to hepatic failure and sepsis; non-fatal complications occurred in 12 patients (26%). Seventeen of the 26 liver transplants were cirrhotic hepatomas. Nine deaths (34%) were caused by technical problems (graft failure, clotting disorder after massive transfusion) and systemic infections. The outcome for the patient after the immediate postoperative period was determined by tumor regrowth (residual liver tissue, graft, distant metastases) in both groups (median life expectancy 18.4 months after radical liver resection and 18.6 months after liver transplantation). Surgery is the only alternative for these patients (50% survival of untreated hepatoma: 2.6 months), improving both their quality of life and survival. We believe that in carefully selected candidates with non-resectable tumors liver replacement may be a useful alternative.

Carcinoma, Hepatocellular↗

[Validation study of the Mannheim Peritonitis Index].

113 patients suffering from purulent peritonitis entered this retrospective study for evaluation of the prognostic value of the Mannheim Peritonitis-Index. There was no lethality below an index x = 21, between x = 21 and x = 29, it was 29% and lethality increased to 100% in patients with an index x greater than or equal to 30. Statistical validation showed that prognosis was correct in 93% for the index x = 27, with a sensitivity and specificity of also 93%. Between x = 21 and x = 29 prognosis of the MPI was correct in at least 65%. The MPI is shown as a prognostic index for peritonitis with high accuracy in individual prognosis, that could be easy routinely documented.

Adolescent↗

Results of surgery for local recurrence of colorectal cancer.

A prospective study was undertaken on the incidence, symptoms, diagnostic measures and therapy of local recurrence of colorectal carcinoma following radical surgical management. 156 (22%) out of 715 patients developed recurrence of the tumour, which was local in 90 patients. In addition, 36 patients with LR from other hospitals were treated. Half of the patients were symptom free at the time of diagnosis. 109 out of the 126 patients were treated by surgery, a radical operation being feasible in 53 cases. 30% of these have survived 36 months. The operative mortality was low (4.6%), although extensive surgery was necessary in most of the cases. The preliminary results of this study support the hypothesis that a postoperative follow-up programme for patients with colorectal cancer leads to early detection of local recurrence and improves the chance of cure by surgical treatment.

Colonic Neoplasms↗

[Consequences of after-care in colorectal cancer].

Results of a computer supported follow-up-program on patients with colorectal cancer are presented. Between 1978 and 1985 1024 patients underwent these program, the drop-out-rate was 18%. 231 recurrences in 137 patients were discovered (40% local recurrence, 30% liver metastases and 30% others). 54% of patients with local recurrence and 43% with liver metastases were free of symptoms. Radical surgery was performed in 47% of local recurrences and in 24% of liver metastases. The three year survival rate after radical surgery for recurrence amounted to 28% for local recurrences and to 31% for liver metastases.

Colonic Neoplasms↗

Isolation and structural analysis of the circulating human cardiodilatin (alpha ANP).

A new method was applied to isolate a polypeptide hormone from human blood. The polypeptides from 1,000 1 of hemofiltrate with a molecular weight lower than 20 kDaltons were adsorbed to 2.5 kg alginic acid, then eluted, precipitated, and desalted on a G-25 Sephadex column, thus obtaining a crude lyophilised plasma polypeptide extract. These polypeptides were further submitted to ion-exchange chromatography. Thereafter, two steps of HPLC were carried out to purify a distinct polypeptide which was the circulating form of cardiodilatin (CDD) in this case. The amino acid analysis, C-terminal enzymatic cleavage by carboxypeptidase A, and sequence analysis showed that the only form of circulating cardiodilatin is the 28 amino acid residue containing molecule, cardiodilatin-99-126 cleaved from the C-terminus of cardiodilatin-126 and identical with alpha-ANP (alpha atrial natriuretic polypeptide). Other bioactive molecular forms of the polypeptide hormones of the cardiodilatin family were not detected in the hemofiltrate. The isolation procedure was followed up by a bioassay using in vitro vascular smooth muscle relaxation.

Amino Acid Sequence↗

Local recurrence of colorectal cancer: effect of early detection and aggressive surgery.

A prospective study was undertaken of the incidence, symptoms, diagnostic measures and therapy of local recurrences of colorectal carcinoma following radical surgical management. Out of 715 patients, 156 (22 per cent) developed recurrence of the tumour, which was local in 90 patients. In addition, 36 patients with local recurrence from other hospitals were treated. Half of the patients were symptom-free at the time of diagnosis. Out of the 126 patients, 109 were treated by surgery, a radical operation being feasible in 53 cases. Fifty per cent of these have survived for at least 17 months. The operative mortality was very low (4.6 per cent), although extensive surgery was necessary in most of the cases. The preliminary results of this study support the hypothesis that a postoperative follow-up programme for patients with colorectal cancer leads to early detection of local recurrence and improves the chance of cure by surgical treatment.

Aged↗

Biochemical characterization of the T-cell mitogen derived from Mycoplasma arthritidis.

A biochemical procedure is described to purify the T-cell mitogen in the supernatant of cultured Mycoplasma arthritidis organisms. The mitogenic material was bound on an affigel blue column. The eluate of this column was then acylated at 0 degrees C for 1.5 h and subsequently chromatography on a Sepharose Cl 6B and a Superose 12HR column were performed. SDS-PAGE showed a major band at MW 26,000 and some minor bands at 50,000. With this material biological tests were performed, including induction of lymphoproliferation and interferon induction in murine spleen cell cultures. Purified Mycoplasma arthritidis supernatant (MAS) vigorously stimulated spleen cell cultures of A/J, CBA, C3H/He, and DBA/2 mice, whereas a low-grade but definitive response was observed in C57BL/6 spleen cells. Cultures of Balb/c nu/nu mice, in contrast to those of their euthymic littermates, were non-reactive. When induction of interferon was tested, a marked response to purified MAS was observed in CBA and C3H/HeJ spleen cell cultures, whereas C57BL/6 spleen cells were non-reactive.

Animals↗

Lymphocyte activation and induction of interferon gamma in human leucocyte cultures by the mitogen in Mycoplasma arthritidis supernatant (MAS).

This report succinctly summarizes a number of experiments in which human leucocytes were activated by the mitogen in the supernatant of cultured Mycoplasma arthritidis (MAS). Lymphocytes from a large number of donors were found to be reactive when the two parameters of lymphoproliferation and of production of gamma interferon were analysed. Lymphocytes of cord blood origin were also reactive in lymphoproliferation. Their interferon production was low, but this has been established previously for mitogens in general. During the course of the studies, different batches of MAS were tested, including most recently a purified preparation. All of these were active. Removal of accessory cells adherent to nylon wool column abolished MAS reactivity, whereas it has little effect on lymphoproliferation induced by phytohaemagglutinin (PHA). MAS reactivity was also strongly reduced when monoclonal anti-HLA-DR antibodies were added to the leucocyte cultures.

Bacterial Proteins↗

The preparation of hydrophilic derivatives of band 3 protein by acylation of the human red blood cell membrane.

In situ reaction of erythrocyte membranes with dicarboxylic anhydrides leads to solubilization of hydrophobic integral proteins. Removal of peripheral proteins and bulk lipid by appropriate sedimentation and dialysis steps yields hydrophilic band 3 protein derivatives. These acyl compounds display size heterogeneity upon gel filtration. A chromatographically homogeneous acyl band 3 protein is obtained if the acylation is conducted in the presence of detergent and the detergent subsequently removed. Hydrophilic acyl derivatives of band 3 protein can be subjected to conventional analytical techniques without the use of detergents.

Acylation↗