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Biomedical subjects

E Bothe

Publications and source records attributed to E Bothe.

At least 37 records · Page 2Linked to original sources
PubMed1990

Single- and double-strand break formation in double-stranded DNA upon nanosecond laser-induced photoionization.

Double-stranded (ds) calf thymus DNA (0.4 mM), excited by 20 ns laser pulses at 248 nm, was studied in deoxygenated aqueous solution at room temperature and pH 6.7 in the presence of a sodium salt (10 mM). The quantum yields for the formation of hydrated electrons (phi c-), single-strand breaks (phi ssb) and double-strand breaks (phi dsb) were determined for various laser pulse intensities (IL). phi c- and phi ssb increase linearly with increasing IL; however, phi ssb has a tendency to reach saturation at high IL (greater than 5 X 10(6) Wcm-2). The ratio phi ssb/phi c-, representing the number of ssb per radical cation, is about 0.08 at IL less than or equal to 5 X 10(6) Wcm-2. For comparison, the number of ssb per OH radical reacting with dsDNA is 0.22. On going from argon to N2O saturation, phi ssb and phi dsb become larger by factors of approximately 5 and 10-15, respectively. This enhancement is produced by attack on DNA bases by OH radicals generated by N2O-scavenging of the photoelectrons. While phi ssb is essentially independent of the dose (Etot), phi dsb depends linearly on Etot in both argon- and N2O-saturated solutions. The linear dependence of phi dsb implies a square dependence of the number of dsb on Etot. This portion of dsb formation is explained by the occurrence of two random ssb, generated within a critical distance (h) in opposite strands. For both argon- and N2O-saturated solutions h was found to be of the order of 40-70 phosphoric acid diester bonds. On addition of electron scavengers such as 2-chloroethanol (or N2O plus t-butanol), phi dsb is similar to that in neat, argon-saturated solutions. Thus, hydrated electrons are not involved in the chemical pathway leading to laser-pulse-induced dsb of DNA.

DNA↗
PubMed1989

[Treatment of newly diagnosed type II diabetic patients with special reference to prescribing glibenclamide in low doses].

In the period of 15 months 90% of all newly registered type II diabetics of a district area (70 males, 122 females) were prospectively thoroughly examined above all in hospital, standardizedly stabilized and have been followed up for 1 year with regard to their therapy behaviour. From the features obtained (age, body weight, heredity, symptomatology, blood glucose and insulin concentrations basally and after 75 g oGTT) subgroupings were worked out relevant for the therapy. 64% of the newly registered type II diabetics could be stabilized purely dietetically (males 70%, females 60.7%). Female type II diabetics revealed the worse course of therapy. Younger age, overweight, genetic load and higher insulin concentrations are markers of the importance of the insulin resistance and a domain of the basis therapy. Older age, normal weight in connection with higher blood glucose and lower insulin concentrations as an expression of the insulin deficit of higher degree render in most cases possible a treatment with SH-preparations. Small doses of glibenclamide proved to be very favourable both in not purely dietetically manageable younger patients and in older patients. 68% of all SH-cases did with a dosage of 1-3 mg glibenclamide a day, 28% with 1 mg a day. The pathophysiologic and pharmacologic mechanisms are discussed.

Aged↗
PubMed1988

Somatostatin-gastrin interactions in the rat stomach.

Low concentrations of somatostatin and gastrin within or slightly above the range of physiologically circulating levels were perfused in the isolated, vascularly perfused rat stomach preparation. Somatostatin at 10 and 50 pg/ml significantly inhibited acetylcholine-stimulated gastrin secretion by 26% and 45%, respectively, whereas perfusion of 50 and 500 pg/ml exogenous gastrin did not modify gastric somatostatin secretion. Perfusion of somatostatin-antiserum significantly increased gastrin release by 235%. It is concluded that (1) somatostatin is a powerful inhibitor of the gastrin cell under in vitro conditions; the data are in accordance with a concept that endogenous somatostatin could act as a true hormone; (2) the secretory activity of the somatostatin cell is not significantly affected by circulating gastrin.

Acetylcholine↗
PubMed1988

Gamma-radiolysis of poly(A) in aqueous solution: efficiency of strand break formation by primary water radicals.

gamma-Radiation-induced single-strand break formation (ssb) in polyadenylic acid (poly(A] has been determined in Ar and N2O-saturated aqueous solution in the presence of different concentrations of t-butanol. Strand breaks were monitored by a low-angle laser light-scattering technique. The efficiencies for strand breakage caused by solvated electrons, hydrogen atoms and OH radicals have been found to be 0.25, 0.20 and 7.8 per cent, respectively. The efficiency of OH radicals depends only slightly on pH (pH 5.0, 7.5 and 9.0) and is independent of the presence of salt (0.01 mol dm-3 NaC1O4) and of the irradiation temperature (20 degrees C and 70 degrees C). The efficiency of OH for ssb formation obtained in this work with poly(A) is much smaller than that of poly(dA). This is explained by the different molecular conformations of the sugar moiety of poly(A) (3'-endo) and poly(dA) (2'-endo). With increasing t-butanol concentration more strand breaks are formed than expected from simple homogeneous competition kinetics of poly(A) and t-butanol for OH radicals. This result is considered to be due to nonhomogeneous reaction kinetics in the above-mentioned competition. The rate constants for the reaction of OH and H with poly(A) have been determined.

Algorithms↗
PubMed1988

Hydroxyl radical-induced strand break formation in single-stranded polynucleotides and single-stranded DNA in aqueous solution as measured by light scattering and by conductivity.

Combining conductivity measurements and molecular weight determination by means of low-angle laser light scattering, we have found for the polyribonucleotides (polyuridylic acid (poly(U], polyadenylic acid (poly(A], polycytidylic acid (poly(C] and polyguanylic acid (poly(G] and for single-stranded DNA (ssDNA) that, on average, 8.5 counterions per single-strand break (ssb) are liberated under salt-free conditions. This relationship allows us to estimate, from conductivity measurements alone, G-values of single-strand break formation (G(ssb] for the polydeoxyribonucleotides (polydeoxyriboadenylic acid (poly(dA], polydeoxyribocytidylic acid (poly(dC], polydeoxyribothymidylic acid (poly(dT], polydeoxyribouridylic acid (poly(dU] and polydeoxyriboguanylic acid (poly(dG]. The following G(ssb) values (units of mumol J-1) have been obtained for anoxic conditions: poly(dA), 0.23; poly(dC), 0.14; poly(dT), 0.06; poly(dU), 0.046 and poly(dG), 0.009. Time-resolved conductivity measurements in pulse radiolysis enable us to measure the rate of strand break formation. The rate has been found to be similar for poly(dA) and ssDNA over a range of pH values. Poly(dC) and poly(dU) exhibit conductivity increase components with half-lives similar to those of poly(dA) and ssDNA at corresponding pH values. The implications of these results are discussed.

DNA Damage↗
PubMed1987

Calcitonin gene-related peptide stimulates rat gastric somatostatin release in vitro.

The influence of rat calcitonin gene-related peptide (rCGRP) on the secretion of gastric somatostatin and gastrin was studied in vitro using the isolated, vascularly perfused rat stomach preparation. rCGRP stimulated somatostatin secretion dose-dependently reaching 3-fold stimulation at 1 microM. The kinetics of somatostatin response were characterized by a sharp increase in the initial phase of rCGRP perfusion followed by sustained elevated levels. Gastrin secretion was moderately suppressed at 1 nM to 100 nM CGRP. Somatostatin responses to half-maximal stimulation with 100 nM CGRP were not affected by concomitant perfusion of atropine, propranolol, and tetrodotoxin. It is concluded that increases in somatostatin release in response to CGRP are probably due to a direct effect on the gastric somatostatin-producing D-cell and may be important for the potent acid-inhibitory activity of CGRP.

Animals↗
PubMed1987

Hydroxyl radical-induced strand break formation of poly(U) in anoxic solution. Effect of dithiothreitol and tetranitromethane.

The role of dithiothreitol (DTT) and tetranitromethane (TNM) on the yields of radiation-induced strand break formation in polyuridylic acid (poly(U] was studied in anoxic aqueous solutions at neutral pH by low-angle laser light-scattering. From G (single-strand breaks) as a function of DTT concentration it follows that two different processes lead to OH radical-induced single-strand break (ssb) formation. Only one of the two processes, which accounts for 80 per cent of the ssb formation, is inhibited by DTT, the other one, 20 per cent, is not inhibited. The 'repair' process is attributed to H-donation to the C-6-yl radical of the uracil moiety. The C-6-yl radical is produced by OH addition to the C-5 position of the uracil moiety. It follows that the sugar radicals, in contrast to earlier suggestions, do not seem to be repaired by DTT at the low concentrations used. The strand break formation not inhibited by DTT is induced by radicals other than the uracil-6-yl radical, e.g. the uracil-5-yl or the OH radicals reacting with the sugar moiety. The strong reduction of G(ssb) from 2.3 to 0.2 on addition of TNM is also discussed.

Chemical Phenomena↗
PubMed1987

Single- and double-strand break formation in DNA irradiated in aqueous solution: dependence on dose and OH radical scavenger concentration.

The yields of single- and double-strand breaks (SSB and DSB) in calf thymus DNA, after 60Co gamma irradiation in dilute aqueous solution, have been determined via molecular weight measurements using a low-angle laser light scattering technique. The irradiations were administered to N2O-containing solutions of DNA in the absence and presence of oxygen and with different concentrations of the OH radical scavengers phenol, tertiary butanol, and methanol. OH radicals were found to produce SSB linearly with dose with a G value of 55 nmol J-1 and 54 nmol J-1 in deoxygenated and oxygenated solutions, respectively. DSB were formed according to a linear-quadratic dose relationship and the G value of linearly formed DSB were GDSB alpha(r.t.) = 3.5 nmol J-1 in deoxygenated and 3.2 nmol J-1 in oxygenated solution. The ratio of GSSB/GDSB alpha(r.t.) = gamma of 19 +/- 6 was independent of the scavenger concentration in the case of tertiary butanol and methanol-containing solutions. GDSB alpha(r.t.) is interpreted to result from a radical site transferred from a sugar moiety of the cleaved strand to the complementary intact strand. This process of radical transfer and subsequent cleavage of the second strand occurs with a probability of about 6 +/- 2% in the presence of oxygen at all scavenger concentrations studied. These data on scavenging capacity on GDSB alpha(r.t.) suggest that the double-strand breakage produced via radical transfer remains higher than that resulting from direct effect, up to scavenging capacities of about 10(9) s-1.

Butanols↗
PubMed1986

Hydroxyl radical-induced strand break formation of poly(U) in the presence of oxygen: comparison of the rates as determined by conductivity, e.s.r. and rapid-mix experiments with a thiol.

The rate of OH radical-induced strand break formation of single-stranded poly(U) in N2O/O2-saturated aqueous solution was studied by measuring the time-dependence of the electrical conductivity following pulse radiolysis. The first half-life of the total conductivity increase depends slightly on pH and the molecular weight and on the dose per pulse. The activation parameters for strand break formation were found to be EA = 52 kJ mol-1 and A = 5 X 10(8) s-1. Similar first half-lives were observed when the decay of peroxyl radicals of poly(U) was measured by e.s.r. under various conditions. This indicates that poly(U)-peroxyl radicals are involved in the rate-determining step of strand break formation. After pulse radiolysis, strand break formation can be inhibited by the addition of dithiothreitol (DTT) in a rapid-mix apparatus. It is postulated that peroxyl radicals of poly(U) react with DTT by formation of hydroperoxides, thereby preventing strand breakage.

Dithiothreitol↗
PubMed1985

Model studies for the direct effect of high-energy irradiation on DNA. Mechanism of strand break formation induced by laser photoionization of poly U in aqueous solution.

Laser flash photolysis of polyuridylic acid (poly U) in anoxic aqueous solutions leads to biphotonic photoionization of the uracil moiety followed by the formation of single strand breaks (ssb). The rate constant for ssb formation (1.0 s-1, obtained from the slow component of conductivity increase at 23 degrees C and pH 6.8) increases with decreasing pH to 235 s-1 at pH 3.5. The activation energy (pre-exponential factor) was measured to be 66 kJ mol-1 (5 X 10(11) s-1) at pH 6.8. Addition of dithiothreitol (DTT) or glutathione (GSH) prevents ssb formation by reacting with a poly U intermediate (rate constant = 1.2 X 10(6) and 0.16 X 10(6) dm3 mol-1 s-1, respectively). Since with OH radicals as initiators very similar data have been obtained for the kinetics of ssb formation and for the reaction with DTT, we conclude that photoionization of the uracil moiety in poly U leads eventually to the same chemical pathway for ssb formation as that induced by OH radicals. Furthermore, we propose that protection by DTT and GSH occurs via H donation to the C-4' radicals of the sugar moiety of DNA and to the C-4' and the C-2' radicals of poly U.

DNA↗
PubMed1984

Yields of radiation-induced main chain scission of poly U in aqueous solution: strand break formation via base radicals.

The G values for single-strand breaks G(ssb) in polyuridylic acid (poly U) have been measured by low-angle laser light scattering in aqueous solutions under various conditions (e.g. in the presence of N2O, Ar and t-butanol). In N2O-saturated solutions at room temperature and pH 5.6, the G(ssb) is 2.3. The efficiency of ssb formation was found to be 41 per cent for OH radicals, 19 per cent for H atoms and congruent to zero for e-aq. On the basis of 20 per cent and less than 5 per cent attack on the sugar moiety by OH radicals and H atoms, respectively, the large G(ssb) values obtained cannot be explained solely as resulting from radicals produced by reaction of OH radicals and H atoms on the sugar moiety. It is therefore proposed that base radicals produced by the reaction of OH radicals or H atoms with the uracil moiety can also lead to chain break formation in poly U via radical transfer to the sugar moiety.

Argon↗
PubMed1983

Adrenergic control of rat gastric somatostatin and gastrin release.

The effect of adrenergic agonists and antagonists on the secretion of gastric somatostatin-like immunoreactivity (SLI) and gastrin was investigated in an isolated, vascularly perfused rat stomach preparation. Two- to six-fold increases in SLI secretion induced by isoproterenol, epinephrine, and norepinephrine were completely abolished by propranolol but were not influenced by phentolamine. Propranolol did not alter glucagon- and DB-cAMP-induced stimulation of SLI release. Experiments in which the beta 2-agonist salbutamol and the beta 1- and beta 2-blockers practolol and H35/25 were used showed that both subtypes of beta receptors are involved. Gastrin secretion revealed only minor changes in dose-response studies with a wide range of isoproterenol concentrations (2 X 10(-8) to 1.5 X 10(-4) M). The results obtained in this study suggest that in rats 1) the SLI response to adrenergic agonism is predominantly mediated by beta receptors; 2) both beta 1- and beta 2-adrenergic receptors are involved; 3) under in vitro conditions, adrenergic agonism is a weak stimulus for gastrin secretion.

Adrenergic beta-Agonists↗
PubMed1982

Adrenergic and cholinergic interactions in rat gastric somatostatin and gastrin release.

The interactions of adrenergic and cholinergic influences on the gastric D cell were studied using an isolated perfused rat stomach in vitro. The sevenfold increase in the release of somatostatin-like immunoreactivity (SLI) in response to isoproterenol (4 . 10(-8) M) was dose-dependently inhibited by acetylcholine (10(-5) to 10(-8) M) whereas gastrin levels increased in a dose-dependent manner. Both inhibition of stimulated SLI and augmentation of gastrin release were completely abolished by atropine (10(-6) M). Isoproterenol (8 . 10(-9) M)-induced stimulation of SLI secretion was not altered by atropine. Antral exclusion completely eliminated gastrin secretion but basal and beta-adrenergic stimulated SLI release was not influenced. It is concluded that (1) cholinergic agonism reverses the stimulatory action of adrenergic agonists on the D cell, and (2) SLI from the rat stomach in vitro originates almost exclusively in the fundic region.

Acetylcholine↗
PubMed1980

Plasma-immunoreactive trypsin in chronic renal failure.

Plasma-immunoreactive trypsin (IRT) was measured by radioimmunoassay in 52 patients with chronic renal failure. 29 were on conservative treatment, 14 on-regular haemodialysis, and 9 on regular haemofiltration. IRT levels were elevated in those with raised plasma creatinine and there was a significant positive correlation to plasma creatinine concentrations (r = 0.853; p less than 0.001). IRT levels were not significantly altered by haemodialysis or haemofiltration. It is concluded that the kidney plays an important role in the metabolism of plasma trypsin. Since plasma IRT levels may be elevated in patients with chronic renal failure, the IRT determination may be misleading in diagnosing acute and chronic pancreatitis in the presence of kidney disease.

Creatinine↗
PubMed1978

Gastrointestinal somatostatin: extraction and radioimmunoassay in different species.

A radioimmunoassay capable of detecting 300 fg somatostatin has been developed and levels of the polypeptide in gastrointestinal tissues from man, dog, and rat have been measured. Rapid freezing of collected samples and careful control of extraction is necessary. Concentrations in different regions of dog antrum (425 +/- 50 to 773 +/- 254 ng/g tissue) are similar to those in antrum from duodenal ulcer patients and control subjects: 614 +/- 125 and 465 +/- 104 ng/g tissue respectively. Levels in histologically normal human pancreas (253 +/- 43 ng/g tissue) are comparable with those in dog pancreas (333 +/- 66 ng/g tissue), whereas in two cases of neonatal hypoglycaemia the concentration exceeded 3000 ng/g tissue. On gel chromatography the majority of immunoreactive somatostatin elutes as the synthetic tetradecapeptide and a small fraction as a larger species.

Animals↗
PubMed1978

[Pancreatic polypeptide (PP) (author's transl)].

Pancreatic polypeptide (PP) can be reproducible measured in serum and tissue extracts by mean of a standardized radioimmunoassay. Dispite extensive investigations into the biological actions of the polypeptide and a range of radioimmunological measurements in serum and tissue the physiological significance of PP is, at present, unclear. The normal postprandial increase of serum PP levels has been reported to be lacking after vagotomy and reduced in patients with chronic pancreatitis. If these observations can be confirmed then PP measurement may be a clinically usefull criterion as to the effectiveness of vagotomy and as an indicator for chronic pancreatic disease.

Digestion↗