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H Steffen

Publications and source records attributed to H Steffen.

At least 55 records · Page 3Linked to original sources
PubMed1994

Effects of synthetic cyclic AMP analogs on amylase exocytosis from rat pancreatic acini.

Diastereomers of adenosine 3',5'-phosphorothioate activate cAMP-dependent protein kinases (cAMP-PK) in vitro. We found that these compounds are highly selective tools to monitor cAMP-dependent PKA activation and its effect on amylase exocytosis from pancreatic acini. In permeabilized rat acinar cells, (Sp)-cAMPS dose-dependently stimulated amylase secretion, while (Rp)-cAMPS inhibited (Sp)-cAMPS-induced amylase release. In intact rat acini, 8-Br-(Rp)-cAMPS reduced the secretory responses to secretin, vasoactive intestinal polypeptide (VIP), 8-Br-cAMP, and 8-Br-(Sp)-cAMPS, but not to cerulein. Another derivative, dibutyryl-(Rp)-cAMPS, induced a small inhibitory effect against 8-Br-(Sp)-cAMPS and VIP, which was overlapped by an unspecific stimulatory effect on amylase exocytosis induced by the degradation product butyrate. Furthermore, (Sp)-5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole-3',5'- monophosphorothioate ((Sp)-5,6-DCl-cBIMPS), a specific cAMP-PK activator, induced a maximal induction of cAMP-PK activity, but its stimulation of amylase secretion was less than that by secretin. (Sp)-5,6-DCl-cBIMPS regulated the phosphorylation of several proteins, which were also affected by secretin. However, secretin had additional effects. Its action was most likely mediated by a dual effect on the cAMP and the calcium pathway. Our results indicate that the cAMP-dependent pathway is involved in amylase exocytosis from rat pancreatic acini.

Amylases↗
PubMed1991

Mixed micelles as a proliposomal, lymphotropic drug carrier.

Four lipophilic, low molecular weight drugs solubilized in phosphatidylcholine-bile salt mixed micelles were injected s.c. into the hind legs of sheep and their cumulative recoveries in lymph draining from the site of application were determined. Surprisingly, the cumulative recoveries (percentage of dose) varied between less than 1 and 60%. We found that there is a correlation between the lipophilicity of the drug (log P octanol/water approximately Rm degrees value) and the proportion of the dose absorbed by the lymphatic route. Drugs with Rm degrees values greater than 10 are absorbed preferentially by the lymphatics (greater than 50% of dose), whereas compounds with Rm degrees values less than 4 are hardly absorbed at all by the lymphatics (less than 10% of dose). By applying the prodrug principle we demonstrated that it is also possible to target drugs with Rm degrees values less than 4 to the lymphatics. Furthermore, the analysis of the collected lymph samples by gel filtration, quasi-elastic light scattering, and electron microscopy revealed that, following s.c. administration, mixed micelles are converted into homogeneous, unilamellar vesicles. In conclusion, these results suggest that mixed micelles may represent a suitable delivery system for low molecular weight drugs whose targets are lymphoid cells. In addition, for drugs where liposomal application leads to a therapeutic advantage, the thermodynamically stable mixed micelle could be a good alternative to the liposome. However, for both applications a high drug lipophilicity is a prerequisite.

Absorption↗
PubMed1990

Effect of molecular weight on the lymphatic absorption of water-soluble compounds following subcutaneous administration.

The lymphatic absorption of four water-soluble compounds with different molecular weights (MW) was determined by measuring their cumulative recovery in lymph draining from the site of s.c. administration in sheep. The cumulative recoveries (% of dose, mean +/- SD; N = 3) were 4.0 +/- 1.5 (5-fluoro-2'-deoxyuridine, MW 246.2), 21.0 +/- 7.1 (inulin, MW 5200), 38.6 +/- 6.7 (cytochrome c, MW 12,300), and 59.5 +/- 7.7 [human recombinant interferon (rIFN) alpha-2a, MW 19,000], respectively. Our data show that in the investigated MW range, there is a linear relationship between the molecular weight and the proportion of the dose absorbed lymphatically. An increase in molecular weight results in an increased lymphatic absorption. Molecules with MW greater than 16,000 are absorbed mainly by the lymphatics which drain the application site. The knowledge gained in this investigation may help to improve the mode of administration and therapeutic efficacy of endogenous proteins whose targets are lymphoid cells (e.g., interferons, interleukins). Practical implications for the clinical use of such proteins are discussed.

Absorption↗
PubMed1988

Repair of the plasmid pBR322 damaged by gamma-irradiation or by restriction endonucleases using different recombination-proficient E. coli strains.

The plasmid pBR322 was treated with BamHI, PvuII and gamma-irradiation to generate double-strand breaks (dsb) containing differently structured ends. Transformation efficiencies, mutation frequencies and clone analyses of enzymatically damaged DNA are compared with the corresponding results from radiolytically damaged DNA. In E. coli K-12 SFX, the yield of transformants produced by the action of BamHI, PvuII and gamma-irradiation (30 Gy) is 4.3%, 0.14%, and 0.10%, respectively. The survival of open circular DNA (ocDNA) produced by 30 Gy is 1.3%. The transformation efficiencies show only a slight dependence on SOS induction and on the RecA protein. Mutation frequencies to tetracycline sensitivity (tets) per surviving plasmid are 2.6% (BamHI), 11.8% (PvuII) and 0.2% (gamma-irradiated DNA with 30 Gy containing approximately 50% ocDNA and 50% linearized (lin) DNA). The mutation frequency is low at all radiation doses studied (1-50 Gy). Only 15% of the DNA of the tets mutants from gamma-irradiated plasmids contained deletions whereas with enzymatically damaged DNA, 30-50% (BamHI) or 90% (PvuII) contained deletions. In all cases, the deletions comprised 500-1700 base pairs (bp). After SOS induction of the host cells, the mutation frequency of gamma-irradiated plasmids increased by a factor of 4, whereas that of the enzymatically damaged plasmids did not change. For the repair of the enzymatically linearized DNA 2 recombinational pathways are discussed which lead to deletant (pathway I) and non-deletant transformants (pathway II). In addition, BamHI-linearized plasmids may be repaired by enzyme-induced or spontaneous circular alignment followed by ligation. The high percentage of deletions of the tets mutations for PvuII-linearized DNA with blunt ends is explained by the illegitimate or site-specific recombination pathway I (see text). The lower percentage of deletions of the tets mutations with BamHI-linearized DNA with short cohesive ends (4 bp) is proposed to be due to a greater contribution of pathway II and/or by circular alignment followed by ligation. The very small yield and the low percentage of deletant mutations of tets mutants from radiolytically damaged DNA is proposed to be due to the large overlapping ends (16-100 bp) of the linDNA which easily leads to circular alignment followed by excision repair. The repair of radiolytically produced ocDNA is predominantly due to excision repair. In agreement with this interpretation is the observation that SOS induction of the host increases the mutation incidence of radiolytically damaged DNA but not of enzymatically damaged DNA.

DNA Repair↗
PubMed1988

Recombinant human interferon alpha-2a: delivery to lymphoid tissue by selected modes of application.

The effect of different parenteral administration routes (i.d., s.c., i.v.), infusion rates, and albumin contents of the drug vehicle on the cumulative recovery of recombinant human interferon alpha-2a (rIFN alpha-2a) in lymph and on its concentration in blood and lymph was determined in sheep. Blood samples were withdrawn from a jugular vein catheter and lymph was collected from a cannulated efferent popliteal lymphatic duct. The concentration of rIFN alpha-2a in lymph and blood plasma samples was measured by an enzyme immunoassay. Following i.v. infusion of 2 x 10(7) U of rIFN alpha-2a, the peak concentrations measured in blood plasma and lymph, respectively, were 8250 and 14 U/ml. The concentration measured in lymph after i.d. or s.c. administration of the same dose was about 10(5) times higher (peak concentration, 3.1 x 10(6) U/ml), while blood plasma levels remained low (peak concentration, 315 U/ml). The cumulative recovery of rIFN alpha-2a in lymph following i.d. or s.c. administration was 59.2 +/- 7% (mean +/- SD; N = 8) and was affected neither by the infusion rate nor by the coadministration of albumin. Our data indicate that following i.d. or s.c. administration, rIFN alpha-2a (MW 19,000) is absorbed mainly by the lymphatics. This results in high levels of rIFN alpha-2a in the lymph which drains from the application site to the regional lymph nodes. The knowledge gained in this investigation may help to improve the mode of administration and therapeutic efficacy of protein drugs whose targets are lymphoid cells.

Absorption↗
PubMed1988

[Peridural administration of analgesics using an implanted Rickham reservoir].

Peridurally administered analgetica provide pain relief and may also be used for treatment of chronic pain of malignant origin. Compared to injection via externalized catheter single-shot injection via implantable reservoir and peridural catheter offers some advantages. The authors have used this method first 1985. Technique of implantation and preliminary results of this method are presented as a case report.

Anesthesia, Epidural↗
PubMed1987

A new heterotopic callosal projection of primary visual cortex in the monkey, Callithrix jacchus.

A callosal projection of area 17 upon the dorsomedial visual area in the marmoset monkey was demonstrated by means of retrograde transport of neuronal tracers. The projection was restricted to those regions representing the vertical meridian in the two areas. This finding, and the data of other authors, indicate that the monkey area 17 projects transcallosally onto homotopic and several heterotopic targets.

Animals↗
PubMed1987

[A new instrument for computerized tomography-guided brain biopsy].

The authors present a new stereotaxic brain biopsy method. After establishment of the CT-and angiographic diagnosis follows the marking of the best suited needle track by means of the CT-scanner Somatom DRG. The trephination is then performed at the operation-theatre during local anesthetization. Repeatedly laying on the CT-table, a low contrasted stereotaxic device is fixed on the patients head. Direction and depth of the puncture are measured and predetermined with an accuracy of +/- 5 mm with a few CT-scans. After guided insertion of a thin-wall nonpaque Teflon-sleeve it is possible to obtain artefactless tomograms or localization control and multiple biopsy probes for histologic evaluation without repeated punctures. Therapeutical interventions may be performed in the same way.

Biopsy, Needle↗
PubMed1984

[Transdural rupture of lumbar intervertebral disk prolapse].

Prolapses of intervertebral disks with intradural localisation are extremely rare. Up to 1981, a total of 41 cases have been published in the world literature. A report is given on two further patients in whom intradural sequesters of intervertebral disks were found during the operation. In one patiente there were at the same time two total intrathecal sequesters from the intervertebral spaces L 3/4 and L 4/5. Until now, no reports have been published on such cases in the world literature.

Cauda Equina↗
PubMed1983

Dose-response study of omeprazole on meal-stimulated gastric acid secretion and gastrin release.

In a placebo-controlled, double-blind, crossover, and randomized trial, the effect of 30, 60, and 90 mg of oral omeprazole on peptone-stimulated gastric acid secretion and synchronously measured gastrin release was studied in 8 healthy subjects. Peptone-stimulated acid output was reduced dose-dependently by 42%, 80%, and 92%, respectively. In spite of a short mean plasma half-life of 52 min, the inhibitory effect lasted for greater than 4.5 h and was significantly correlated to the area under the plasma concentration time curve for omeprazole. Mean basal serum gastrin and gastrin profiles increased insignificantly without alteration of integrated gastrin output and did not show any correlation either to the omeprazole area under the plasma concentration time curve or to the inhibition of peptone-stimulated acid secretion. Side effects, significant alterations of laboratory screen, or alterations of serum concentrations of thyroid hormones were not detected. In conclusion, omeprazole is a potent and, under the conditions tested, well-tolerated inhibitor of meal-stimulated gastric acid secretion in humans.

Adult↗
PubMed1983

[Urine pseudocyst following multiple injury with closed subpelvic ureteral rupture in childhood].

The authors discuss special aspects concerning children and traffic accidents, prompted by the frequency of such accidents. They present a model of the pathogenesis of closed injuries of the ureter. On the basis of the mechanics of accidents and clinical experience, closed subpelvic rupture of the ureter is to be seen as the result of a deceleration trauma. Problems of the treatment of patients with multiple injuries and the diagnosis and therapy of closed injuries of the ureter are presented on the basis of a clinical observation.

Accidents, Traffic↗
PubMed1981

[Microsurgical anastomoses between extra- and intracranial arteries (author's transl)].

86 patients underwent microanastomoses to branches of the anterior-, medial-and posterior cerebral arteries and the inferior cerebellar artery. Intraoperative electromagnetic measurement yielded a mean flow of 33 ml/min with a velocity of 11 to 54 cm/s. The brain circulation increased by a percentage of 38. In a percentage of 90 postoperative angiographic controls turned out anastomoses to be patent. By this surgical technique unilateral brain circulation can be improved significantly.

Arteries↗
PubMed1980

Steroidogenic action of calcium ions in isolated adrenocortical cells.

The corticotropin-induced increase of total intracellular and receptor-bound cyclic AMP in isolated rat adrenocortical cells was strictly dependent on extracellular Ca(2+). A rise in bound cyclic AMP with rising Ca(2+) concentrations was accompanied by a decrease in free cyclic AMP-receptor sites. A Ca(2+)-transport inhibitor abolished the rise in bound cyclic AMP induced by corticotropin. These data suggested that during stimulation by corticotropin some Ca(2+) has to be taken up in order to promote the rise of the relevant cyclic AMP pool. In agreement with this view, adenylate cyclase activity from isolated cells proved also to be dependent on a sub-millimolar Ca(2+) concentration in the presence of corticotropin and GTP. When cells were treated under specific conditions, corticosterone production could be activated by Ca(2+) in the absence of corticotropin (cells primed for Ca(2+)). Ca(2+)-induced steroidogenesis of these cells, in the absence of corticotropin, was also accompanied by an increase in total intracellular and receptor-bound cyclic AMP, as was found previously with corticotropin-induced steroidogenesis in non-primed cells. Calcium ionophores increasing the cell uptake of Ca(2+) were not able, however, to increase the cyclic AMP pools in non-primed cells, unlike corticotropin in nonprimed cells or Ca(2+) in cells primed for Ca(2+). It was concluded that during stimulation by either corticotropin or Ca(2+) a possible cellular uptake of Ca(2+) must be very limited and directed to a specific site which may affect the coupling of the hormone-receptor-adenylate cyclase complex.

Adenylyl Cyclases↗
PubMed1980

Early lesions of mouse vibrissal follicles:: their influence on dendrite orientation in the cortical barrelfield.

There is a statistically significant order in the tangential orientation of stellate cell dendrites, both spiny and smooth, in layer IV of the barrelfield of the mouse parietal cortex. Neurones situated in a barrel side have most of their dendrites oriented towards the barrel hollow; those situated in the hollow preferentially orient their dendrites parallel to the long axis of the barrel. A quantitative measure of the orientation of individual dendrites in barrelfields of 60-day old mice was obtained using a semi-automatic computer-microscope and a minicomputer. In the same manner, the dendrite orientation of layer IV stellate cells was determined in barrelfields, whose (cytoarchitectonic) pattern had been experimentally altered through lesions of the middle row of the mystacial vibrissal follicles at birth. The dendrites of these cells are oriented in harmony with the novel parcellation of the cortex. Consequently, for cells in the altered areas of the barrelfields, the dendrite orientation is different from that of cells with identical positions in a normal field (see Fig. 8). We tentatively interpret these findings as an adaptation of dendrite orientation to an altered pattern of thalamic input to layer IV that, in turn, is a consequence of the peripheral manipulation.

Animals↗