Biomedical subjects

W Forssmann

Publications and source records attributed to W Forssmann.

10 recordsLinked to original sources

PubMed2001

The renal urodilatin system: clinical implications.

A renal natriuretic peptide and the 'renal urodilatin system' were identified after the observation that immunoassayable ANP in urine may not be identical to the circulating cardiac hormone ANP, which is a peptide of 28 amino acids. Urodilatin (INN: Ularitide) is a natriuretic peptide isolated from human urine and belongs to the family of A-type natriuretic peptides. Urodilatin is differentially processed to a peptide of 32 amino acids from the same precursor as ANP. It is synthesized in kidney tubular cells and secreted luminally. After secretion from epithelial cells of the distal and/or connecting tubules, Urodilatin interacts downstream at distal segments of the nephron with luminally located receptors whereby it regulates Na(+) and water reabsorption. Thus, the physiological function of the renal Urodilatin system can be described as a paracrine intrarenal regulator for Na(+) and water homeostasis, considering Urodilatin as a real diuretic-natriuretic regulatory peptide. However, the regulation upon which the Urodilatin secretion depends is still not clear. Since Urodilatin has been discovered, a great number of pharmacological and clinical investigations have been carried out using Urodilatin as a drug for several indications. So far, clinical phase I and II studies for acute renal failure, congestive heart failure, and bronchial asthma have been performed.

Animals↗

PubMed2000

The human PER1 gene is transcriptionally regulated by multiple signaling pathways.

The mammalian period (Per) genes are components of the circadian clock and appear to be regulated via an autoregulatory feedback loop. Here we show that the human PER1 (hPER1) gene is synergistically activated by protein kinases A and C (PKA, PKC) and cAMP responsive element binding protein. Activators and inhibitors of PKA as well as PKC modulate endogenous hPER1 expression and hPER1 promoter-driven reporter gene activity in a dose-dependent manner. Our results suggest that the hPER1 promoter acts as a sensor for multiple signaling molecules thereby integrating different physiological parameters. This regulation of hPER1 appears to be significant for rapid adaptation to changing environmental conditions.

Cell Cycle Proteins↗

PubMed1999

Variability in the ratio of mutant to wildtype myosin heavy chain present in the soleus muscle of patients with familial hypertrophic cardiomyopathy. A new approach for the quantification of mutant to wildtype protein.

The ratio of mutant to wildtype myosin heavy chain (beta-isoform, beta-MHC) in the soleus muscle of patients with familial hypertrophic cardiomyopathy was determined by a combination of HPLC, mass spectrometry and capillary zone electrophoresis. In two patients, one with a Val 606 Met mutation and another with a Gly 584 Arg mutation, the fraction of mutant beta-MHC was only 12+/-6% and 23+/-0.7% of total beta-MHC, respectively. These results demonstrate the necessity to determine the ratio of mutant to wildtype protein for the interpretation of functional studies on biopsy material from heterozygous patients with an inherited disease.

Amino Acid Substitution↗

PubMed1998

Equine cardiodilatin/ atrial natriuretic peptide. Primary structure and immunohistochemical localization in auricular cardiocytes.

Cardiodilatin (CDD)/atrial natriuretic peptide (ANP) is a 28-amino acid peptide hormone known to be synthesized in the heart of a large number of different vertebrates. It plays an important role in the regulation of blood pressure and natriuresis/diuresis. Since the cardiovascular system of the horse has to meet the highest requirements concerning its physiological performance, we intended to characterize the cardiodilatin/atrial natriuretic peptide system of this species. By means of immunohistochemistry and immunoelectron microscopy, we precisely identified auricular cardiocytes as the loci of CDD/ANP synthesis. Using aortic smooth muscle relaxation assay and CDD/ANP-ELISA, we succeeded in isolating the biologically active prohormone. We subsequently cloned the equine cDNA of the CDD/ANP precursor protein and deduced its primary sequence. The entire precursor protein is in good agreement with the CDD/ANP prohormones of other mammals. The deduced theoretical average Mr of equine CDD/ANP-1-126 is 13,764, corresponding to the molecular weight of purified peptide determined by ESI-MS. Our findings suggest that equine CDD/ANP is produced in auricular cardiocytes and the predominant storage form of CDD/ANP in the auricle is the prohormone CDD/ANP-1-126.

Amino Acid Sequence↗

PubMed1997

Gene expression of aphrodisin in female hamster genital tract segments.

Aphrodisin is a glycoprotein originally isolated from hamster vaginal discharge which was demonstrated to be involved in pheromonal effects on male hamsters. In the present study, we investigated the localization of aphrodisin-synthesizing and -storing cells in the entire genital tract of the female golden hamster using immunohistochemical and molecular biological methods. By use of immunohistochemical methods, significant aphrodisin immunoreactivity was detected within the cervical glandular tissue. Western blot analysis revealed high concentration of aphrodisin in vaginal discharge and in tissue extracts from the vagina and the cervix uteri. According to intracellular localization of aphrodisin, this protein is confined to cytoplasm of the immunoreactive cells. Immunoreactivity was also detected extracellularly on the surface of the anterior vaginal pluristratified epithelium. Semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis showed an extremely high level of aphrodisin gene expression in the vagina and in the lower part of the uterus comprising the cervix. However, aphrodisin gene expression was also demonstrated in the middle part of the uterus and at a low level even in the ovaries. No aphrodisin gene expression was detectable in the upper part of the uterus and the uterine horns. In situ hybridization confirmed that the maximum expression of the aphrodisin gene is encountered in glandular cells of the cervix uteri. These results indicate that within the female hamster genital tract aphrodisin is predominantly synthesized throughout the vagina and cervical uterus. The protein is then secreted into the vaginal lumen. It is under discussion whether the accumulation of aphrodisin in the vaginal discharge facilitates the transfer of pheromone of low molecular weight to the male hamster's vomeronasal organ during investigatory behavior.

Amino Acid Sequence↗

PubMed1968