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Biomedical subjects

R Gerzer

Publications and source records attributed to R Gerzer.

At least 55 records · Page 3Linked to original sources
PubMed1995

Health care in remote areas.

Migration from space medicine toward telemedicine services is described by potential application areas in highly populated and remote areas of Europe. Special emphasis is laid upon links between mobile patient monitoring and health care in remote areas. Pilot projects are described for home (mobile) monitoring of newborn infants endangered by sudden infant death (SID) and adults suffering from sleep apnoea. Health care in remote areas is described by the "TeleClinic-project" which will link national nodes for telemedicine services in several European states for the mobile European citizen. Another project describes the future potential of robotics for semiautonomous ultrasound diagnostics and for realtime interaction of remote experts with diagnostics and therapy.

Adult↗
PubMed1995

A non-isotopic immunoassay for guanosine 3':5'-cyclic monophosphate using a cyclic GMP-biotin conjugate as tracer.

2'-O-monosuccinylguanosine 3':5'-cyclic monophosphate was coupled to N-biotinyl-1,8-diamino-3,6-dioxaoctane after converting succinyl-cGMP into its N-hydroxysuccinimide active ester. Isolation and purification of the succinyl-cGMP-biotin conjugate was performed with FPLC using reversed phase chromatography. The synthesis described yielded a conjugate suitable for use as tracer in immunoassays for the cGMP measurement in plasma and urine samples. Employing biotin as the primary probe in a competitive solid phase immunoassay allows for flexible end point determination by means of commercially available labeled streptavidin derivatives. Streptavidin-europium was used in conjunction with the DELFIA-system for time-resolved fluorometric end point measurement (TR-FIA), streptavidin-horseradish peroxidase was used for colorimetric end point determination (EIA). Both non radioactive immunoassay systems showed excellent correlation with the reference radioimmunoassay, good sensitivity and reproducibility. The succinyl-cGMP-biotin conjugate was shown to be stable for more than two years without any apparent loss of chemical stability or immunological reactivity.

Biotin↗
PubMed1995

Severe hypotension and bradycardia after continuous intravenous infusion of urodilatin (ANP 95-126) in a patient with congestive heart failure.

The effects of a continuous i.v. infusion of urodilatin at a dose of 30 ng kg-1 min-1 were studied in a patient with congestive heart failure. After 30 min, urodilatin had induced a marked stimulation of plasma cyclic GMP concentrations. In parallel haematocrit increased. No significant diuresis and no change of invasive haemodynamics was observed. After 2 h the patient developed a profuse perspiration. Eighty minutes later he suffered from dizziness due to hypotension (blood pressure 80/40 mmHg) and a sudden bradycardia (50 bpm). Urodilatin was discontinued and symptoms were relieved by bed tilt and rapid infusion of isotonic saline solution. Mechanisms contributing to these adverse effects may be fluid extravasation to the third space and sympathoinhibitory effects known to occur with natriuretic peptide infusion.

Atrial Natriuretic Factor↗
PubMed1995

The volume protective natriuretic peptide system in the inner ear. Comparison between vestibular and cochlear compartments.

It has been suggested that the family of natriuretic peptides (NP) has a protective role in volume overloading. Specific binding sites for atrial natriuretic peptide (ANP) and the kidney analog urodilatin (URO) were identified and quantified with computerized autoradiography and biochemical assay in the cryosection in the cochlear and vestibular (utricle/ampulla) tissue. Immunohistochemistry was used to identify and localize NP-like immunoreactive cells. Different levels of specific receptors between and within the inner ear compartments were detected. The presence of specific receptors for NP, as well as unequal distribution of NP-immunoreactivity between the compartments (in certain parts of the cochlea and the endolymphatic sac), may indicate a local autocrine and/or paracrine action of these peptide systems (presumably as a result of the integration of the different peptide effects), independent of their action via the more conventional systemic route, in addition to differences in response of the inner ear compartments to the load. The present results on specific binding of ANP and URO in the inner ear tissue may suggest physiological homology between the inner ear and the kidney. Moreover, a similar role of NP in these organs is suggested.

Atrial Natriuretic Factor↗
PubMed1994

Distinction of weakly homologous cDNA amplificates by single-strand conformation polymorphism analysis: application to guanylyl cyclase isozymes.

By use of the polymerase chain reaction (PCR), uniform amplification products of 225 to 240 bp length were obtained from five cDNA clones representing different types of guanylyl cyclases. These short DNA double strands were differentiated by single-strand conformation polymorphism (SSCP), using polyacrylamide gel electrophoresis with the Pharmacia Phast-System. Following heat denaturation, the samples were separated on native polyacrylamide gels at different running temperatures. Nucleic acids on the gel were detected by an automated silver stain procedure. Using 7.5% homogeneous or 4-15% gradient polyacrylamide gels at a temperature of 12 degrees C, single-strand conformations of amplificates, representing three different particulate guanylyl cyclases and the two subunits of soluble guanylyl cyclase, were differentiated. The characteristic banding patterns resulting from dissimilar migration of the single-strand conformations were assigned to different guanylyl cyclase types. For the enzyme family of guanylyl cyclases, the feasibility of a combined PCR and electrophoresis approach for analyzing the expression of related genes was demonstrated. This application of the PCR-SSCP technique provided a rapid and sensitive tool for the characterization of PCR products obtained with a common primer pair and suggested its use for investigating the tissue distribution of gene expression within a class of homologous proteins.

Animals↗
PubMed1994

Antinatriuretic kidney response to weightlessness.

We have tested the effects of weightlessness on renal function in one subject who flew the recent week-long Russian-German MIR'92 space mission. Urine flow, renal sodium excretion, and the excretion of urodilatin were measured during the first and last days of the flight. Our results demonstrated, in contrast to expectations, that urine flow and sodium excretion during weightlessness were actually lower than the values obtained during preflight measurements. These results therefore are inconsistent with the commonly held hypothesis that weightlessness induces a diuresis and natriuresis in human subjects. It would seem that further studies are necessary to resolve this issue and to determine whether currently used ground-based models of weightlessness correctly predict physiological adaptations that occur during space flight.

Atrial Natriuretic Factor↗
PubMed1994

Natriuresis in conscious dogs caused by increased carotid [Na+] during angiotensin II and aldosterone blockade.

The renal response to a selective increase in the Na+ concentration of the blood perfusing the central nervous system was investigated in conscious dogs treated with the converting enzyme inhibitor enalaprilat and the aldosterone antagonist canrenoate. In split-infusion experiments the plasma [Na+] of carotid blood was increased (approx. 6 mM) by bilateral infusion of hypertonic NaC1. Concomitantly distilled water was infused into the v. cava making the sum of the infusions isotonic. In control experiments isotonic saline was infused at identical rates into all three catheters. Na+ excretion increased markedly in both series, 103 +/- 14 to 678 +/- 84 mumol min-1 during split-infusion and 90 +2- 14 to 496 +/- 74 mumol min-1 during the isotonic volume expansion. Peak rate of excretion, peak fractional sodium excretion, and cumulative sodium excretion were all significantly higher (P < 0.05) during split-infusion than during control experiments. Plasma vasopressin increased only during split-infusion (0.68 +/- 0.11 to 2.4 +/- 0.8 pg ml-1) while the increases in plasma atrial natriuretic peptide were similar in the two series. Urinary excretion of urodilatin (ANP95-126) increased significantly more during split-infusion (46 +/- 11 to 152 +/- 28 fmol min-1) than during the isotonic volume expansion (45 +/- 14 to 84 +/- 16 fmol min-1) (P < 0.05). It is concluded that the natriuretic mechanisms activated by a selective increase in the Na+ concentration of carotid blood and associated with increased excretion of urodilatin cannot be eliminated by blockade of the renin-angiotensin-aldosterone system.

Angiotensin II↗
PubMed1994

Distribution of membrane bound guanylyl cyclases in human intestine.

The quantification and distinction of particulate guanylyl cyclases in the human intestine were considered by an enzymatic approach, which comprised the signal transduction from receptor binding to cGMP formation, and, in addition, by showing the expression of an intracellular portion of these transmembrane proteins. Basal guanylyl cyclase (GC) activities were 50 to 80 pmol cGMP formation/min/mg protein and were stimulated up to twofold by heat stable enterotoxin, but were not significantly influenced by atrial natriuretic factor. Enzymatic analysis of colonoscopic specimens pointed to the prevalence of guanylyl cyclase C in the terminal ileum and in the large bowel including colon ascendens, colon descendens, sigmoid, and rectum. The availability of sequence information on human guanylyl cyclases permitted the development of a polymerase chain reaction approach for distinguishing the expression of GC-A and GC-C in human tissue samples. The expression levels of particulate guanylyl cyclases found by polymerase chain reaction in surgical biopsy specimens confirmed the enzymatic data, in that substantial expression of GC-C was found not only in the small intestine but also in the large bowel. According to the restriction mapping of amplificates, GC-C prevailed over GC-A throughout the human intestine, particularly in the mucosal layers.

Adult↗
PubMed1994

Effect of water temperature on diuresis-natriuresis: AVP, ANP, and urodilatin during immersion in men.

Effects of water temperature on diuresis, natriuresis, and associated endocrine responses during head-out immersion were studied in eight men (23.4 +/- 0.3 yr) during four 5-h experimental conditions: air control at 28 degrees C and immersion at 34.5 degrees C [thermoneutral (Tnt)], 36 degrees C [above Tnt (aTnt)], and 32 degrees C [below Tnt (bTnt)]. Esophageal temperature decreased by approximately 0.4 degrees C in bTnt and increased by approximately 0.5 degrees C in aTnt. Cardiac output increased by approximately 80% in aTnt and approximately 40% in bTnt while thoracic impedance, an index of central blood pooling, decreased by 7.5 omega in bTnt (NS vs. Tnt) and 8.8 omega in aTnt (P < 0.05 vs. Tnt and bTnt). Total peripheral resistance decreased at all temperatures (50% in aTnt, 20% in bTnt). Urine flow and Na+ excretion increased by sixfold in bTnt and Tnt but by only threefold in aTnt. Creatinine clearance was unchanged while osmolal clearance (but not free water clearance) increased two-fold with all immersions. Plasma atrial natriuretic peptide (ANP), urinary urodilatin, and urinary guanosine 3',5'-cyclic monophosphate increased while plasma renin activity, aldosterone, and arginine vasopressin (AVP) decreased similarly at all temperatures. bTnt did not potentiate diuresis by selective attenuation of AVP. The overall natriuretic response exhibited a higher correlation with urodilatin (r = 0.45, P < 0.001) than with ANP (r = 0.26, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Influence of the cGMP analog 8-PCPT-cGMP on agonist-induced increases in cytosolic ionized Ca2+ and on aggregation of human platelets.

The present study was undertaken to compare inhibitory effects of the cGMP analog 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate (8-PCPT-cGMP) on increases in cytosolic ionized Ca2+ and on aggregation in human platelets induced via diverse agonists. Fura-2-loaded and gel-filtered platelets were stimulated by either ADP (8 microM), thrombin (0.025 IU/ml) or collagen (1-3 micrograms/ml), respectively. The cGMP analog induced a concentration-dependent inhibition of cytosolic ionized Ca2+ increases and of aggregation to all agonists investigated with half-maximal inhibiting effects of approximately 100 microM. The data obtained suggest that both platelet Ca2+ exchange and aggregation have a similar sensitivity to the cGMP analog. In accordance with previously found significant differences between the potencies of nitric oxide (NO)-generating substances to inhibit increases in cytosolic ionized Ca2+ and aggregation, it appears that the antiplatelet effects of NO-releasing agents could only partially be explained by the elevation of cGMP levels.

Adenosine Diphosphate↗
PubMed1993

The circulating bioactive form of human guanylin is a high molecular weight peptide (10.3 kDa).

Guanylin is a peptide isolated from rat intestine that stimulates intestinal guanylate cyclase. We describe here the purification of circulating guanylin from human hemofiltrate. By N-terminal protein sequence analysis 47 amino acids were determined. This sequence corresponds to the positions 22 to 68 of the prohormone deduced from the cDNA sequence of human proguanylin. Mass spectral analysis of the circulating peptide showed the molecular weight to be 10,336 Da, which corresponds to the mass calculated from position 22 to the C-terminus of the peptide predicted from the cDNA sequence. Circulating guanylin markedly increased the cyclic GMP content of T84 cells. Our data show that the hormonal form of guanylin is circulating as a 10.3-kDa peptide in human blood.

Amino Acid Sequence↗
PubMed1993

Effects of nitric oxide-containing compounds on increases in cytosolic ionized Ca2+ and on aggregation of human platelets.

The present study was undertaken to determine the modulatory effects of nitric oxide (NO)-releasing compounds on increases in cytosolic ionized calcium ([Ca2+]i) and on aggregation of gel-filtered human platelets induced via diverse agonists. We used various sydnonimines and organic nitrates as donors of NO. Gel-filtered and fura-2-loaded platelets were stimulated with ADP (4-8 microM), collagen (2-10 micrograms/ml) or thrombin (0.02-0.05 IU/ml), respectively. Half-maximal inhibiting effects of sydnonimines on agonist-evoked increases in [Ca2+]i were observed between 30 and 1000 nM, while half-maximal inhibiting effects of the compounds on aggregation were between 3 and 500 nM. The compound C 87-3754, which is the bioactive metabolite of pirsidomine, was a much stronger inhibitor of increases in [Ca2+]i than of platelet aggregation. This was due to an enhanced NO release from this compound exposed to ultraviolet light during Ca2+ measurement. The organic nitrates isosorbide 5-mono-nitrate and nicorandil inhibited both aggregation and increase of cytosolic ionized calcium in stimulated platelets at half-maximal concentrations of approximately 200 microM. The present results suggest that some of the effects of NO on platelets are independent of cytosolic ionized calcium. The results also suggest that some of the inhibitory effects of NO-releasing compounds correspond rather to the presence of the A forms (NO-containing intermediates) than to the presence of free NO.

Calcium↗
PubMed1993

Reduced natriuresis during weightlessness.

The kidney response to weightlessness was measured in one volunteer during a 1-week space mission. Shortly after entering microgravity and later during the mission, consecutive urine sampling periods were monitored, covering in total about 50% of the inflight time. Preflight references were a sequence of ground-based experiments, which evaluated body fluid metabolism with different degrees of standardization. Additional variables, such as circadian rhythms and cortisol-associated stress, were also monitored. In contrast to current hypotheses, the volunteer showed a pronounced reduction in natriuresis and diuresis during the entire space flight, despite a considerable weight loss. For the first time, the urinary excretion of the renal natriuretic peptide urodilatin was also measured. Both, during the preflight experiments and during weightlessness, close correlations between urodilatin excretion and sodium excretion were observed. However, the correlation between natriuresis and urodilatin excretion was considerably altered during weightlessness. We conclude that the loss of body weight during space flight is not related to an increased renal fluid loss and that urodilatin might counteract the decrease in renal excretion observed in weightlessness.

Atrial Natriuretic Factor↗
PubMed1993

Long-term elevations of dietary sodium produce parallel increases in the renal excretion of urodilatin and sodium.

The effects of dietary sodium intake on the renal excretion of urodilatin and of sodium were examined in six healthy male subjects. The 24-day study period was divided into three phases of 8 days each. Subjects ingested 2.8 mequiv sodium (kg body weight)-1 day-1 during the first phase, 5.6 mequiv (kg body weight)-1 day-1 during the second phase, and 8.4 mequiv (kg body weight)-1 day-1 during the third phase. The excretion of both sodium (P < 0.002) and urodilatin (P < 0.006) increased in response to the increasing dietary sodium, while urine flow did not change. Urinary urodilatin excretion correlated closely with renal sodium excretion (P < 0.001). Serum aldosterone levels (P < 0.01) as well as serum renin levels (P < 0.05) significantly decreased with increasing sodium intake. Plasma [Arg]vasopressin levels increased significantly (P < 0.05). Plasma atrial natriuretic factor and cGMP levels as well as urinary cGMP excretion rates were unaltered by the changes in sodium intake. We conclude from these results that the renal natriuretic peptide, urodilatin, but not the main cardiac member of the natriuretic peptide family may be involved in the regulation of day-to-day sodium balance.

Adult↗
PubMed1993

Development and application of a urodilatin (CDD/ANP-95-126)-specific radioimmunoassay.

Urodilatin, a renal natriuretic peptide that is an analogue to circulating atrial natriuretic peptide [alpha-ANP(99-126)], is measurable with a highly specific and sensitive radioimmunoassay. While most ANP antibodies cannot distinguish between urodilatin and other ANP analogues, the polyclonal urodilatin antibody specifically measures human urodilatin without any cross-reactivity to other ANP analogues. Urodilatin is not detected in blood from healthy volunteers nor from cardiac patients. Urinary urodilatin accounts for only a part of total urinary ANP immunoreactivity. Urodilatin excretion closely parallels sodium excretion in response to an acute volume load while changes in urinary immunoreactive ANP excretion do not reflect this renal response. We conclude that specific urodilatin assays are required to explore further the physiological role of the renal natriuretic peptide.

Amino Acid Sequence↗