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Biomedical subjects

R Götz

Publications and source records attributed to R Götz.

At least 19 recordsLinked to original sources
PubMed1995

Parathyroid hormone secretion and serum calcium concentration--a deterministic view of its regulation.

In seven normal men we investigated the basal secretion of PTH by blood sampling in 30 sec intervals for estimation of intact PTH and at 2-min intervals for measurement of ionized calcium. In 4 of these subjects we also investigated the PTH-secretion under conditions of intermittent hypercalcemia and hypocalcemia. Our measurements demonstrate the existence of three time scales in the secretion of PTH, viz. short-term pulses (faster than 2 min), an intermediate pattern of adjusting PTH levels to changed Ca2+ averages, and finally a long-term coupling between PTH and Ca2+ averages after 20 min. Ionized calcium controls the long-term regulation and intermediate adaptation mechanisms, but the short-term fluctuations seem to be due to spontaneous secretion.

Adult↗
PubMed1995

The complete nucleotide sequence and genome organization of the mite-transmitted brome streak mosaic rymovirus in comparison with those of potyviruses.

A virus isolate, designated as 11-Cal, originating from southern France has been identified as an isolate of the mite-transmitted brome streak mosaic rymovirus (BrSMV) by serological and morphological properties. BrSMV is a member of the genus Rymovirus of the family Potyviridae. The complete nucleotide sequence of the RNA genome of BrSMV has been determined. The assembled RNA is 9672 nucleotides in length, excluding a 3'-terminal poly(A)sequence. The RNA contains one open reading frame (ORF) of 9282 nucleotides coding for a polyprotein of 3093 amino acids. A comparison with typical potyvirus showed that BrSMV has a similar genome organization. The predicted cleavage sites of the polyprotein of BrSMV are similar to those of potyviruses. Nevertheless, unusual dipeptides are proposed in two cases. Based on the proposed location of the cleavage sites nine mature proteins are predicted. Specific motifs, described for potyviral polyproteins, are almost all present in the polyprotein of BrSMV, too. However, only an incomplete zinc-finger motif is present in the potential helper component and the motif for aphid transmission in the coat protein is not found. Several alignments of amino acid sequences showed less similarity between BrSMV and potyviruses than between different potyviruses.

Amino Acid Sequence↗
PubMed1994

Toxic acute renal failure in the rat: effects of L-arginine and N-methyl-L-arginine on renal function.

Nitric oxide (NO) is generated from L-arginine (Arg) by different isoforms of nitric oxide synthase (NOS) and plays a major role in maintaining the high basal renal blood flow. NO also is involved in the regulation of glomerular haemodynamics and contractility of mesangial cells. We examined the hypothesis that L-arginine-derived NO modifies toxic ARF in the rat. After a basal period uranyl nitrate (UN) was given intravenously as a bolus injection (25 mg/kg over 5 min) to induce ARF. After the initiation phase of ARF (3 h) saline in the control group (C) and drugs in the experimental groups (I-III, each n = 8) were administered for 60 min. Group I, Arg (300 mg/kg); group II, MeArg (30 mg/kg); group III, Arg + MeArg (300 mg/kg, 30 mg/kg resp.). The experiments were continued for further 60 min following the infusion period. Glomerular filtration rate (GFR, inulin clearance) was reduced 3 h after UN to about 50% of normal values in groups I-III and control group (I, 0.52 +/- 0.06; II, 0.51 +/- 0.05; III, 0.49 +/- 0.05; C, 0.50 +/- 0.07 ml/min). After infusion of Arg GFR had significantly improved (0.64 +/- 0.07), but further declined after MeArg (0.46 +/- 0.06) in relation to control (0.47 +/- 0.07). This negative effect could be overcome by combined administration of Arg + MeArg (0.59 +/- 0.07). One hour after the infusion period these effects were even more pronounced (Arg, 0.71 +/- 0.06; MeArg, 0.43 +/- 0.05; Arg + MeArg, 0.65 +/- 0.07; C, 0.46 +/- 0.05). We conclude that the L-arginine/NO pathway is involved in toxic ARF of the rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1992

Production and characterization of recombinant mouse neurotrophin-3.

Neurotrophin-3 (NT-3) is a neurotrophic-factor that has recently been cloned on the basis of its structural similarity to other members of the nerve growth factor (NGF) gene family. In order to produce this protein, a recombinant vaccinia virus containing the coding region for mouse NT-3 was constructed. Conditioned medium harvested from cells infected with the recombinant vaccinia virus contained biologically active NT-3 that was purified by chromatography on controlled-pore glass and reversed-phase and gel-filtration high-pressure liquid chromatography. Approximately 200 micrograms purified NT-3 was obtained from a single cell-factory flask (1.6 1 conditioned medium). N-terminal protein sequencing showed that the mature factor was processed from the precursor at the expected site and its amino acid composition agreed with that predicted from the DNA sequence. The biological activity of the recombinant protein was tested on dissociated neurons prepared from chick embryos. Using spinal sensory neurons, the concentration of purified recombinant NT-3 allowing half-maximal survival was determined to be 25 pg/ml.

Amino Acids↗
PubMed1992

Binding of neurotrophin-3 to its neuronal receptors and interactions with nerve growth factor and brain-derived neurotrophic factor.

Neurotrophin-3 (NT-3) has low-affinity (Kd = 8 x 10(-10) M), as well as high-affinity receptors (Kd = 1.8 x 10(-11) M) on embryonic chick sensory neurons, the latter in surprisingly high numbers. Like the structurally related proteins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), NT-3 also binds to the low-affinity NGF receptor, a molecule that we suggest to designate low-affinity neurotrophin receptor (LANR). NT-3 dissociates from the LANR much more rapidly than BDNF, and more slowly than NGF. The binding of labelled NT-3 to the LANR can be reduced by half using a concentration of BDNF corresponding to the Kd of BDNF to the LANR. In contrast, the binding of NT-3 to its high-affinity neuronal receptors can only be prevented by BDNF or NGF when used at concentrations several thousand-fold higher than those corresponding to their Kd to their high-affinity neuronal receptors. Thus, specific high-affinity NT-3 receptors exist on sensory neurons that can readily discriminate between three structurally related ligands. These findings, including the remarkable property of the LANR to bind three related ligands with similar affinity, but different rate constants, are discussed.

Animals↗
PubMed1992

[Pharmacokinetics of gadolinium-DTPA in chronic renal insufficiency requiring dialysis].

MRT with gadolinium-DTPA (0.1 mmol/kg body weight) was performed in 10 patients with renal insufficiency requiring dialysis and the clearance of gadolinium-DTPA was studied. After 3 dialysis on 3 successive days more than 97% of the initial concentration of gadolinium-DTPA had been eliminated. Average half-life was 1.87 hours. There were no side effects in any of the patients. Close laboratory observation of liver function showed no significant changes during the period of study. No contra-indication for the use of this contrast medium in patients with renal insufficiency requiring dialysis was found during this study.

Adult↗
PubMed1992

Brain-derived neurotrophic factor is more highly conserved in structure and function than nerve growth factor during vertebrate evolution.

Mammalian nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are members of a protein family with perfectly conserved domains arranged around the cysteine residues thought to stabilize an invariant three-dimensional scaffold in addition to distinct sequence motifs that convey different neuronal functions. To study their structural and functional conservation during evolution, we have compared NGF and BDNF from a lower vertebrate, the teleost fish Xiphophorus, with the mammalian homologues. Genomic clones encoding fish NGF and BDNF were isolated by cross-hybridization using probes from the cloned mammalian factors. Fish NGF and BDNF were expressed by means of recombinant vaccinia viruses, purified, and their neuronal survival specificities for different classes of neurons were found to mirror those of the mammalian factors. The half-maximal survival concentration for chick sensory neurons was 60 pg/ml for both fish and mammalian purified recombinant BDNF. However, the activity of recombinant fish NGF on both chick sensory and sympathetic neurons was 6 ng/ml, 75-fold lower than that of mouse NGF. The different functional conservation of NGF and BDNF is also reflected in their structures. The DNA-deduced amino acid sequences of processed mature fish NGF and BDNF showed, compared to mouse, 63% and 90% identity, respectively, indicating that NGF had reached an optimized structure later than BDNF. The retrograde extrapolation of these data indicates that NGF and BDNF evolved at strikingly different rates from a common ancestral gene about 600 million years ago. By RNA gel blot analysis NGF mRNA was detected during late embryonic development; BDNF was present in adult brain.

Amino Acid Sequence↗
PubMed1991

[Changes in renal function in heart failure and their modification by conversion enzyme inhibitors].

In congestive heart failure renal hemodynamics are characterized by a decrease of fractional renal blood flow (renal fraction of the cardiac output) and marked changes of the intrarenal circulation. The latter consists of cortical hypocirculation and an enhanced medullary blood flow in the presence of a relative rise in glomerular filtration rate (GFR). This compensatory increment of GFR is mediated by a stimulation of prostaglandins (dilatation of vas afferens) as well as the renin-angiotensin- and adrenergic systems (contraction of vas efferens). Therapy with ACE inhibitors influences renal function in a complex manner. A decline in GFR resulting in the worst case in acute renal failure (ARF) may be caused by two pathogenetic possibilities: 1. critical reduction in renal perfusion pressure (below 70 mm Hg) and/or 2. loss of the autoregulation of GFR by relaxation of the constricted vas efferens induced by stimulation of the renin-angiotensin-systems (RAS). Activation of the RAS might be a consequence of severe renal hypocirculation as well as a diuretic induced volume and sodium depletion (contraction of the effective arterial blood volume). On the other hand, ACE inhibitors may improve renal blood flow and glomerular filtration rate. This may be due to a rise in cardiac output, dilatation of vas efferens and occasionally vas afferens and an increase of the ultrafiltration coefficient. The deterioration of renal function caused by ACE-inhibitors may be prevented by avoiding a volume and sodium deficit (withdrawal or reduction of diuretics) and careful titration of the ACE-inhibitor starting with lowest dosages.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

[Regulation of thirst in end-stage kidney insufficiency].

About 30% of hemodialyzed patients are suffering from chronic fluid overload despite advice to restrict the oral fluid intake. To investigate the cause of the abnormal drinking behaviour a clinical study was performed in 51 non-diabetic patients with endstage renal disease exhibiting lower interdialysis weight gain (less than 3 kg, n = 17) and increased interdialysis weight gain (greater than 3 kg, n = 34). Blood pressure, body weight self-estimated thirst intensity before and after hemodialysis were analyzed. Biochemical and behavioral variables were measured including hormonal factors of water and sodium metabolism. Significant differences of dry weight, creatinine, urea nitrogen and thirst intensity were found between the two groups. Catecholamines, renin, angiotensin II, aldosterone, vasopressin and atrial natriuretic peptide exhibited a similar pattern in both groups. Atrial natriuretic peptide decreased during hemodialysis in both groups, angiotensin II, however, and norepinephrine showed an exaggerated response to ultrafiltration rate in polydipsic patients. These results suggest that changes in serum osmolality during hemodialysis did not contribute to thirst and drinking behaviour. It seems that postdialytic hypovolaemia together with higher plasma-angiotensin II-levels is responsible for increased oral intake of fluid and excessive weight gain.

Angiotensin II↗
PubMed1990

[Dilatation and balloon-expandable stents for the treatment of central venous stenosis in dialysis patients].

On 10 dialysis patients we performed 12 balloon dilatations, 2 catheter lyses, 6 stent implants (Palmaz stent) and one atherectomy of central venous stenoses or occlusions (v. subclavia, v. brachiocephalica) at the shunt arm of the patient. The primary success rate was, in balloon PTA and lysis, 12/14 interventions, and in stent placement and atherectomy 7/7. The angiographical and clinical primary result after stent implantation was significantly better than after conventional dilatation. After 66% of the balloon dilatations recidivation occurred within the first year; this can be treated by means of repeated PTA. Whether long-term exclusion of recurrence can be achieved by stent implantation, must be established by means of follow-up studies that are at present in progress.

Adult↗
PubMed1990

Impaired response to intrarenal administered atrial natriuretic peptide in ischemic acute renal failure of a transplanted patient.

A 30-year-old male patient suffering from membrano-proliferative glomerulonephritis was transplanted a cadaveric kidney 3 years ago. Five days later the transplant was removed because of fresh thrombosis in larger arteries. Three years after first transplantation a second graft was transplanted. Repeated perfusion scintigraphies of persistent anuric patient showed a delayed perfusion of renal parenchyma, no intrarenal bolus was obtained. Urgently, an arterial angiography was performed. It demonstrated that calibers of renal parenchymal vasculature were narrowed. Suggesting ischemic nature of acute renal failure, 50 micrograms human atrial natriuretic peptide (hANP) was injected intrarenally as bolus. Five minutes after hANP injection in a second angiography a significant improvement of renal blood flow was demonstrated but no amelioration of urine production or electrolyte excretion was observed. Histologically an ischemic lesion of transplant was proven. This finding indicates a blunted excretory response of acute renal failure after kidney transplantation despite of significantly ameliorated renal blood flow visualized radiologically.

Acute Kidney Injury↗
PubMed1990

Atrial natriuretic peptide reverses experimental acute renal failure induced by arginine vasopressin.

Recently, it has been reported that atrial natriuretic peptide (ANP) reverses or prevents acute renal failure induced by norepinephrine in rats. Therefore, we tested the hypothesis that vasoconstrictor doses of arginine vasopressin (VP) can induce renal ischemia and that consequent renal dysfunction is reversed by ANP infusion or bolus injections in rats. Intrarenally infused VP produced a significant decrease of glomerular filtration rate (GFR) and an increase of urinary volume and sodium excretion rate. Systemic blood pressure increased significantly during VP administration. In a second experimental period, ANP was also given intrarenally, control rats received isotonic saline solution. ANP infusion revealed a highly significant increment of GFR, urinary volume and sodium excretion. Blood pressure fell down below values of the preperiod. After cessation of ANP infusion, renal function was reduced again. These results indicate that VP induces a nonoliguric acute renal failure which is reversed by ANP infusion but only at the time of its administration.

Acute Kidney Injury↗
PubMed1990

Angiotensin-converting enzyme inhibition in renal and hypertensive disorders.

Angiotensin-converting enzyme (ACE) inhibitors have been available for about 10 years for the treatment of various forms of hypertension. Essential hypertension responds particularly well to the administration of this group of drugs, especially when combined with diuretics. A pronounced fall in blood pressure can be achieved in renovascular hypertension with high plasma renin levels; when ACE inhibitors were administered in diagnosed renal artery stenosis there was a significant rise in plasma renin activity on the affected side. Renoparenchymatous hypertension and hypertension in diabetes mellitus can also be improved by the long-term administration of ACE inhibitors, and the progression of renal failure in these disorders seems to be slowed down. Side effects such as neutropenia, exanthema, hearing disorders and pronounced hypotension with an acute deterioration in renal function are substance- and dose-dependent; regular monitoring of the patients greatly reduces their occurrence.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Plasma clearance of bile acids in the rat: hepatic uptake under physiological conditions without countertransport.

Studies in rats by others indicated that sulfobromophthalein (BSP), bilirubin and indocyanine green are taken up by the liver and can be transported back to plasma against the prevailing concentration gradient (= countertransport). The present in vivo study was designed to determine whether the bile acids cholic acid and taurocholic acid under physiological conditions undergo appreciable countertransport as has been suggested by experiments in isolated hepatocytes. Experiments with BSP (controls) showed that injections of unlabeled BSP into rats five minutes after the administration of radiolabeled BSP was followed by a release of radioactivity into plasma (BSP-countertransport). In contrast bile acid countertransport could not be demonstrated, no matter whether it was tested 1, 5 or 8 minutes after the administration of radiolabeled cholic- or taurocholic acid.

Animals↗
PubMed1988

[Atypical Caroli syndrome with kidney failure in cystic renal changes].

In a 61-year-old man in terminal renal failure from bilateral renal polycystic degeneration abdominal sonography chanced to demonstrate in the left lobe of the liver a saccular, pearl string-like dilatation of the, at first no further definable, duct systems. Hepatobiliary scintigraphy revealed them to be bile-draining and thus confirmed Caroli's disease, which had previously been asymptomatic for any hepatic involvement. Since in the majority of cases of Caroli's disease renal changes are symptom-free associated findings, the question arises whether in this case there is the coexistence of polycystic renal disease and Caroli's disease or whether the biliary tract and renal changes constitute a nosological entity in the sense of atypical Caroli's disease.

Bile Duct Diseases↗