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Biomedical subjects

R Henning

Publications and source records attributed to R Henning.

At least 37 records · Page 2Linked to original sources
PubMed1991

Difficulties encountered in transport of the critically ill child.

A prospective survey of difficulties encountered in 100 pediatric emergency interhospital transfers was undertaken to identify needs for education of referring doctors and of transport service staff, as well as weaknesses in the organization of a pediatric emergency transport service (PETS). Such obstacles to smooth retrieval included administrative difficulties, mistakes in management, and unresolved acute severe physiologic derangements in the child. Three hundred ninety-four problems were found: 24% were preventable by improved education of referring doctors; these included unrecognized needs for ventilatory support, added oxygen, chest x-ray or nasogastric tube, and difficulties with airway selection, placement, and care. Twenty-eight percent were preventable by better PETS organization, education, protocols, or telephone checklists; examples include equipment problems and clinical derangements unrecognized at referral. Difficulties owing to conditions of transport (eg. vibration, dysbarism, and air turbulence) were uncommon (five percent of patients). Regular reviews of performance of all PET services, combined with measures to educate referring doctors, can improve patient outcome.

Child↗
PubMed1989

Ventilator-dependent children.

The issue of the ventilator-dependent child is a relatively-new one in Australia. Ventilator-dependent children pose complex and unique ethical, medical, economic and psychological problems. The experience of two Australian centres that are involved with the care of ventilator-dependent children is reported. Most of these children now are being cared for at home. Aspects of home care are outlined. After the initial period, the technical aspects are not a problem for most parents for whom the major issues are the provision and funding of nursing support. The complex ethical issues that are involved are discussed. It is concluded that undergoing ventilation at home rather than in a hospital appears to make the best of an otherwise almost-intolerable situation for ventilator-dependent children, but that much more information is required about the outcome for these children and the long-term psychosocial impact of this treatment.

Adolescent↗
PubMed1989

Bioconstruction of the extrahepatic biliary duct system in minipigs. Comparing normal condition with experimental obstruction.

The extrahepatic biliary duct system is subject to a particular bioconstruction to secure its bile transport function. The dominant structure of the bile duct wall is a network of collagen fibres harboring muscle-fibre bundles. The collagen fibres are virtually inelastic, volumes can be changed only by rearranging the network. The ducts show different spatial arrangements of the fibres causing different extents of dilatation during obstruction. Extreme dilatation might cause a rupture of the network, and deficient postoperative retonisation could be the result.

Animals↗
PubMed1989

Inhibition of converting enzyme in brain tissue and cerebrospinal fluid of rats following chronic oral treatment with the converting enzyme inhibitors ramipril and Hoe 288.

A direct central nervous system (CNS)-related component of the cardiovascular actions of converting enzyme (CE) inhibitors will be governed by the ability of these drugs to gain access to the brain. We investigated the inhibitory effect of the two CE inhibitors ramipril and Hoe 288 on CE activity in different brain regions and in the cerebrospinal fluid of rats. One-week oral gavage treatment with ramipril (10 mg/kg/day) and Hoe 288 (10 mg/kg/day) resulted in a marked inhibition of CE activity in the brain cortex (90 and 91%, respectively), the hypothalamus (78 and 82%, respectively), and in the brainstem (67 and 66%, respectively). The complete blockade of plasma CE activity was paralleled by a 84% inhibition of CE activity in cerebrospinal fluid. Both CE inhibitors failed significantly to inhibit CE activity in the striatum. Our results demonstrate that the CE inhibitors Hoe 288 and ramipril were able to pass the blood-brain barrier (BBB) to inhibit central CE activity. The penetration of CE inhibitors into the CNS appears to depend on the lipophilicity of the drugs and on the mode of drug application. The possibility that an inhibition of CE activity in circumventricular organs outside the BBB such as the subfornical organ and the organum vasculosum of the lamina terminalis may be sufficient to explain the central effects of orally applied CE inhibitors is discussed.

Administration, Oral↗
PubMed1988

Evidence for a distinct Ca2+ antagonist receptor for the novel benzothiazinone compound HOE 166.

The pharmacological and binding properties of the novel enantiomerically pure benzothiazinone (R)-(+)-3,4-dihydro-2-isopropyl-4-methyl-2-[2-[4-[4-[2-(3,4,5-tri- methoxyphenyl)-ethyl]-piperazinyl]-butoxyl-phenyl]-2H-1,4- benzothiazine-3-one dihydrochloride (HOE 166), are described. HOE 166 stereoselectively inhibited KCl-but not noradrenaline-induced contractions of guinea-pig pulmonary arteries, rabbit aorta, rat mesenteric artery preparations and k-strophantin-induced enhancement of guinea-pig papillary muscle contraction in a dose-dependent manner. KCl-induced smooth muscle contraction was inhibited by HOE 166 with IC50-values of approximately 70 nM (5-11 times less potent than nifedipine, 2-16 times more potent than verapamil), the respective S-(-)-enantiomer being approximately 10-fold less potent. HOE 166 decreased the upstroke velocity of the slow action potential in partially depolarized guinea-pig papillary muscle at similar concentrations than nifedipine. To investigate possible interactions with the calcium channel, HOE 166 and its S-(-)-enantiomer were characterized by radioligand binding studies in heart, brain and skeletal muscle transverse-tubule membranes. HOE 166 was a 4-15 times more potent inhibitor of reversible (+)-[3H]PN200-110, (-)-[3H]desmethoxyverapamil and d-cis [3H]diltiazem binding compared to its pharmacologically less active (S)-(-)-enantiomer, with IC50 values in the low nanomolar range. Extensive equilibrium and kinetic studies suggest that HOE 166 exerts its Ca2+-antagonistic effect by binding to a Ca2+-channel-associated drug receptor which is distinct from the 1,4-dihydropyridine, phenylalkylamine or benzothiazepine-selective domain. This HOE 166-selective site is, however, allosterically linked to the other sites of the Ca2+ antagonist receptor complex. We conclude that HOE 166 is a novel calcium antagonist.

Action Potentials↗
PubMed1988

A novel high affinity class of Ca2+ channel blockers.

Benzolactams (HOE 166 and analogs) form a new class of molecules acting on the 1,4-dihydropyridine-sensitive L-type Ca2+ channels. The main binding properties of HOE 166 and analogs to rabbit skeletal muscle membranes are as follows. (i) The compounds have a specific binding site to which they associate with a high affinity (0.25 nM for HOE 166). (ii) Unlabeled HOE 166 and analogs completely inhibit 1,4-dihydropyridine binding [(+)-[3H]PN 200-110] in a competitive way. (iii) Affinity values measured for HOE 166 inhibition of (+)-[3H]PN 200-110 (K0.5 = 0.25 nM and K1 = 0.55 nM) and of [3H]HOE 166 binding (K0.5 = 0.5 nM) are in good agreement. They also fit with results from direct binding experiments with tritiated HOE 166 (Kd = 0.27 nM) and from kinetic experiments (Kd = 0.39 nM). (iv) HOE 166 completely inhibits the specific binding of other classes of Ca2+ channel antagonists such as phenylalkylamines [(-)[3H] desmethoxyverapamil], benzothiazepines (d-cis-[3H]diltiazem), diphenylbutylpiperidines ([3H]fluspirilene), and [3H]bepridil. In all these cases the binding inhibition is of a noncompetitive nature. (v) The maximum binding capacity for [3H]HOE 166 binding to transverse tubule membranes, 65 pmol/mg of protein, is the same as that found for other classes of Ca2+ channel antagonists. 45Ca2+ uptake experiments performed with the rat aortic cell line A7r5 and the insulin-secreting cell line RINm5F demonstrate that HOE 166 and analogs fully inhibit the 1,4-dihydropyridine-sensitive 45Ca2+ influx elicited by depolarization. There is a good correlation between inhibitory potencies of compounds in the HOE 166 series measured on (+)-[3H]PN 200-110 binding to A7r5 membranes and on the activity of Ca2+ channels followed by 45Ca2+ fluxes with the same cells. Structure-function relationships of HOE 166 and analogs for Ca2+ channel blockade in A7r5 and RINm5F cells were also in good correlation. Finally, voltage-clamp experiments confirmed that voltage-dependent L-type Ca2+ channels are completely blocked by 100 nM HOE 166 even at a membrane potential held at -80 mV.

Animals↗
PubMed1987

Comparison of nitroglycerin-TTS and long-acting nitroglycerin tablets in the treatment of angina pectoris: a double-blind controlled study.

A cohort of 99 patients with severe, stable angina pectoris participated in a 26-week double-blind, between-patient trial of a transdermal therapeutic system (TTS) Nitroglycerin-TTS 5 mg/24 h and long-acting nitroglycerin tablets, 10.4 mg daily. The variables registered included daily sublingual nitroglycerin requirement, daily anginal attack rate, exercise test performance with ECG recordings, and a subjective patient evaluation on a visual analogue scale. There were no significant differences in the efficacy of the treatment between the two groups. Nor could we find any difference in the efficacy between the initial single-blind placebo treatment and the active nitroglycerin treatments.

Administration, Cutaneous↗
PubMed1987

Enhanced protein phosphorylation in SV40-transformed and -infected cells.

We have studied the phosphorylation of cellular phosphoproteins and, in more detail, of SV40 T antigen and the cellular protein p53 in SV40 tsA-transformed cells. As detected by radiolabeling cold-sensitive tsA1499- or heat-sensitive tsA58-transformed rat fibroblasts with [32P]orthophosphate or by in vitro labeling extracts with [gamma-32P]ATP the hyperphosphorylation of certain cellular phosphoproteins including p53 and also of free SV40 large T antigen and T antigen complexed with p53 is strictly correlated with the expression of the transformed phenotype. This hyperphosphorylation can be observed as early as 30 min after shifting to the temperature where the cells expressed the transformed phenotype and, furthermore, it is dependent on protein synthesis. To evaluate the influence of a functional T antigen and to exclude properties of individual transformants we 32P labeled in vitro cellular proteins from rat F111, mouse NIH 3T3, and monkey TC-7 cells infected with tsA58 or tsA1499. In tsA58-infected cells we found a heat-sensitive enhancement of protein phosphorylation just as in tsA58 transformants. In tsA1499-infected monkey cells we observed a heat-sensitive and in abortively infected rat or mouse cells a cold-sensitive hyperphosphorylation of proteins. Thus in tsA-transformants and in various tsA-infected cells we found a strong correlation among the transformed phenotype, functions of T antigen, and the phosphorylation of various cellular proteins and in particular T antigen and p53.

Animals↗
PubMed1987

The AT-rich sequence of the SV40 control region influences the binding of SV40 T antigen to binding sites II and III.

During lytic infection SV40 T antigen binds specifically to three different regions of the SV40 DNA to initiate DNA replication and to regulate early and late transcription. We constructed plasmids containing either 23-bp synthetic oligonucleotides representing site I or II or SV40 DNA fragments with combinations of binding sites II and III with or without SV40 specific flanking regions. These plasmids were used to determine which sequences are sufficient for specific binding to isolated regions II and III. Under identical conditions T antigen bound in a sensitive in vitro binding assay efficiently to site I but not to the corresponding oligonucleotide of site II. Binding to site II could only be observed in the presence of the adjacent 17-bp AT-rich region of the SV40 DNA. On account of the markedly low affinity for binding site II, T antigen concentrations were required which exceeded those necessary to achieve saturation of binding to site I. The very low affinity for isolated site III could be slightly raised by the same AT-rich region. An increased binding to site II at 37 degrees compared to 0 degree in the presence of this region points to an indirect influence on the DNA structure of the binding site.

Animals↗
PubMed1987

Synthesis and neuroleptic activity of a series of 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]benzim idazolone derivatives.

A series of 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]benzimid azolones with various substituents in both aromatic rings have been synthesized and tested for neuroleptic activity (antiapomorphine effects and [3H]spiroperidol binding) as well as extrapyramidal effects (cataleptogenic effect). A strong dependence of activity on the 5-substituent in the benzimidazolone moiety could be demonstrated. Some compounds show a large split between the desired antiapomorphine and the undesired extrapyramidal effect. From these, 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]-5-chlor obenzimidazol-2-one hydrochloride (HR 723), 12, has been selected for further preclinical and toxicological profiling.

Animals↗
PubMed1986

Regions of SV40 large T antigen necessary for oligomerization and complex formation with the cellular oncoprotein p53.

The simian virus 40 (SV40) T antigen is composed of 708 amino acids and forms monomers and various oligomers and, in small amounts, heterologous complexes with the cellular oncoprotein p53 (T-p53). Using SV40 mutants coding for T antigen fragments which are either deleted in the N-terminal half or truncated by various lengths at the C-terminal end, we found that a region between amino acids 114 and 152 and a C-terminal region up to amino acid 669 are essential for the formation of high Mr oligomers of T antigen. Furthermore, only the C-terminal end up to amino acid 669 is essential for T-p53 complex formation but not the N-terminus up to amino acid 152.

Amino Acid Sequence↗
PubMed1986

Complex formation of simian virus 40 large T antigen with cellular protein p53.

We investigated the formation of native complexes between simian virus 40 large T antigen and the cellular protein p53 (T-p53) by using simian virus 40 tsA58-transformed mouse fibroblasts (tsA58 F2b). We observed that newly synthesized p53 bound to all structural subclasses of large T antigen detectable on sucrose density gradients. This led to various intermediates of T-p53 complexes which converted within 2 h into typical mature aggregates. The final levels of stable T-p53 complexes seemed to be determined by p53 rather than by large T antigen.

Animals↗
PubMed1986

Clinical applications of mechanical ventilation.

This paper reviews recent applications of mechanical ventilation such as controlled hypoventilation in acute asthma, domiciliary nocturnal ventilation in chronic respiratory failure due to neuromuscular disease and improvement of left ventricular performance by raised intrathoracic pressure. Established uses of mechanical ventilation include control of respiratory failure, intracranial pressure and pulmonary hypertension while other uses such as internal splinting of flail chest, simultaneous ventilation-compression cardiopulmonary resuscitation and prophylactic postoperative ventilation are more controversial.

Anesthesia, General↗
PubMed1985

Oligomerization of simian virus 40 tumor antigen may be involved in viral DNA replication.

Biological implications of the oligomerization of simian virus 40 (SV40) large T antigen for viral DNA replication were studied by using two temperature-sensitive SV40 A-gene mutants, tsA 58 and tsA 1499. Both mutants are defective at elevated temperature for viral DNA replication whereas tsA 58 is like most other tsA mutants additionally heat sensitive for cell transformation. We found that in contrast to tsA 58 encoded T antigen, tsA 1499 T antigen is thermostable in the ability to bind specifically to the origin of replication of SV40 DNA. Detailed structural analysis of tsA 1499 T antigen by sucrose density gradient centrifugation revealed that it is strictly temperature sensitive for the formation of homologous oligomers but, as we reported previously (M. Montenarh, M. Kohler, and R. Henning, 1984, J. Virol, 49, 658-664), not for the association with the cellular phosphoprotein p53. These observations are compatible with the idea that, in addition to the specific origin-binding ability as well as other functional features, the oligomerization of T antigen may be essential for viral DNA replication.

Animals↗
PubMed1985

Relationship of phosphorylation to the oligomerization of SV40 T antigen and its association with p53.

The potential significance of the phosphorylation of SV40 large T antigen for oligomers and complexes with the cellular protein p53 was investigated. We observed that T antigen oligomers remain stable after enzymatic dephosphorylation by alkaline phosphatase up to 80%. Separate analysis of free and p53-bound T antigen revealed a considerably lower phosphorylation of the p53-bound subclass. Therefore, a simple correlation between the overall phosphorylation of T antigen and the formation of oligomers and T-p53 complexes is highly unlikely.

Antigens, Polyomavirus Transforming↗
PubMed1985

Structural prerequisites of simian virus 40 large T antigen for the maintenance of cell transformation.

We have investigated the functional roles of two structural subsets of simian virus 40 (SV40) large T antigen, namely homo-oligomers and complexes with the host cellular p53 protein, for the transformed phenotype. We examined T antigen produced in cells transformed by temperature-sensitive SV40 large T mutants: heat-sensitive or unrestricted SV40 tsA58-transformed rat cells and unrestricted tsA1499 transformants. In both unrestricted cell lines, T antigen was temperature-sensitive only for the formation of fast sedimenting homo-oligomers. Corresponding to our recent observations obtained with tsA1499-infected monkey cells, in tsA1499 transformants large T was competent to form stable T-p53 complexes independently of the temperature. However, T antigen coded for by tsA58, which is heat-sensitive for binding to p53, occurred in stable complexes with this protein in unrestricted tsA58 transformants under all conditions. Furthermore, in both unrestricted transformants T-p53 complexes arise in the absence of homo-oligomers of T antigen. In conclusion, T antigen homo-oligomers are not involved in cell transformation, whereas T-p53 complexes may be involved in the maintenance of this phenotype.

Animals↗