Showing papers by "University of Basel published in 1975"

Control of cell-contact sites by cyclic AMP pulses in differentiating Dictyostelium cells.

Abstract: SINGLE cells of the slime mould Dictyostelium discoideum differentiate after the end of the growth phase of their life cycle into interacting cells which form aggregates by chemotaxis towards a source of cyclic AMP1,2, with the formation of specific contacts between cells3–5. Emergence into the aggregation phase coincides with an increase in the number of specific contact sites (known as contact sites A; ref. 3) on the surface of the cells. The appearance of contact sites A is thus an index of differentiation and we have used it to test the hypothesis that cyclic AMP is a signal for initiating differentiation6,7, as well as acting as the aggregation signal for differentiated cells.

Antihypertensive beta blocking action as related to renin and age: a pharmacologic tool to identify pathogenetic mechanisms in essential hypertension.

Abstract: Three hundred fifteen patients with essential hypertension were classified according to low (18 percent), normal (59 percent) or high (23 percent) renin-sodium index. The proportion of patients with low renin hypertension progressively increased with increasing age and blood pressure, there being no difference between the sexes. Two high renin groups emerged: a younger group with early moderate hypertension, and an older group with severe hypertension consequent to possibly ischemic renal disease. Long-term beta blocking monotherapy in 137 patients resulted in a reduction of idastolic pressure to 95 mm Hg or less in 65 percent: 85 percent in those with high and 73 percent in those with normal renin activity; pressure was reduced to this level in only 1 of 24 patients (4 percent) with a low renin index. Antihypertensive efficacy was also related to age, since diastolic pressure was normalized in 80 percent of patients under age 40 years, in 50 percent of those aged 40 to 60 years, but in only 20 percent of those over age 60 years. Age may heolp in patient selection but is no substitute for the more reliable renin index, especially in patients over age 40 years, or with high pressure. Using studiew with propranolol as a standard, similar renin responses were obtained with two cardioselective beta1 type blocking drugs, atenolol and metoprolol, as well as with two nonselective beta2+1 receptor antagonists, LL21945 exhibiting prolonged receptor affinity and oxprenolol in slow release form. These long-acting drugs, which proved effective in single daily doses, could be of value in improving patient compliance...

A Quantitative Assessment of „Through-space”︁ and „Through-bond”︁ Interactions. Application to Semi-empirical SCF Models

Abstract: The scheme of ‘through-space’ and ‘through-bond’ interaction of (semi)localized orbitals, originally proposed by Hoffmann, is reexamined in terms of SCF many-electron treatments. It is shown that the two types of interaction can be characterized by examining the corresponding off-diagonal matrix elements of the Hartree-Fock matrices of the localized or the symmetry adapted localized orbitals and of the partially diagonalized Hartree-Fock matrices referring to ‘precanonical orbitals’. The procedure outlined is applied to three practical examples using the semiempirical many-electron treatments SPINDO, MINDO/2 and CNDO/2: a A reassessment of ‘through-space’ and ‘through-bond’ interaction in norbornadiene indicates, that the latter type of interaction is also of importance for the orbital based mainly on the antisymmetric combination of the localized x-orbitals. The differences in the predictions derived from the three models are critically examined. b The competition between ‘through-space’ and ‘through-bond’ interaction in the series of bicyclic dienes from norbornadiene to bicyclo[4.2.2]-dcca-7,9-diene and in cyclohexa-1,4-diene, i. e. their dependence on the dihedral angle UI is reexamined. It is found that the rationalization for the orbital crossing near ω = 130° deduccd from PE. spectroscopic data can not be as simple as originally suggested and that the relay’ orbitals responsible for ‘through-bond interaction affecting both the symmetric and the antisymmetric combination of the π-orbitals extend over the whole CC-σ-system of the six membered ring. c ‘Through-bond’ interaction of the two lone pair orbitals in 1,4-diazabicyclo[2.2.2]octane is found to be large for their symmetric and the antisymmetric linear combination. The analysis quoted, draws attention to some of the dangers involved in using semiempirical treatments for the interpretation of PE. data in terms of Koopmans′ theorem, without due caution.

The tryptophan synthase from Escherichia coli. An improved purification procedure for the alpha-subunit and binding studies with substrate analogues.

Abstract: An improved method is described for the purification of the α-subunit of tryptophan synthase from Escherichia coli. The standard manganese chloride and acid-precipitation steps have been replaced by rapid and efficient chromatographic procedures. Indoleethanol phosphate, indolepropanol phosphate and indolebutanol phosphate have been synthesized. They are not cleaved by tryptophan synthase and are strictly competitivee inhibitors versus indoleglycerol phosphate. The inhibition constant decreases as the number of methylene groups in the side chain increases. This may reflect an improved accommodation of the indole and phosphate moieties to their respective subsites. The difference spectra generated by binding indole, indoleglycerol phosphate and indolepropanol phosphate to the α-subunit are very similar. This reflects the transfer of the indole moiety to an hydrophobic environment within the active center. The binding of indolepropanol phosphate to the α2β2-complex perturbs the spectrum of pyridoxal 5′-phosphate located in the β2-subunit. This demonstrates direct or indirect interactions between the component active sites. Binding studies by spectrophotometric titration and equilibrium dialysis with indolepropanol [32P]phosphate show that there is only one binding site per equivalent of α-subunit. Complex formation with the β2-subunit increases the affinity of the α-subunit for indolepropanol phosphate. It is a general consequence of protein-protein interaction in this system.

Chemical analysis and electron microscopy studies of human C1q prepared by different methods.

Abstract: Five differently isolated and purified human C1q preparations were examined by electron microscopy and analyzed by polyacrylamide gel electrophoresis in 0.1% sodium dodecyl sulfate and 0.5 M urea. The amino acid and carbohydrate composition of C1q purified by the DNA method are reported and compared with results obtained on C1q isolated by other procedures. Electron microscopy showed that all C1q preparations had six peripheral subunits connected by fibrillar strands to a central subunit. The presence of small amounts of dimers was also observed. The physico-chemical properties of the molecule are independent of the purification method used. The five C1q preparations labeled with 125I in presence of lactoperoxidase formed two types of noncovalently linked subunits. In each case the smaller (central) subunit contained over thirty times as much radioactivity as the larger (peripheral) subunit supposed to interact with immune complexes. Reduction and alkylation confirmed for each preparation the presence of three polypeptide chains, the smaller of which contained essentially all radioactivity.

The role of macrophages in the generation of T helper cells. III. Influence of macrophage-derived factors in helper cell induction.

Abstract: Helper cell induction to soluble or particulate antigens in vitro requires the cooperation of T cells and macrophages. A direct contact between macrophages and T cells is not obligatory for this cooperation and factors released from macrophages are as effective in activating T cells as the cells themselves. Two different types of macrophage-derived factors where found. The supernatant obtained from purified macrophages incubated with antigen for several days generates helper cells in absence of macrophages or additional antigen, but only if obtained from macrophages which were identical at the I-A subregion of the H-2 complex as the T cells. This factor was called genetically related macrophages factor (GRF). The other factor(s), which is present in the supernatant obtained from macrophages incubated for several days without antigen, replaces macrophages only if the antigen is particulate. This factor(s), called nonspecific macrophage factor (NMF) is not restricted genetically and is also obtained from allogeneic macrophages. The importance of both these factors in helper cell induction is discussed.

Role of macrophages in in vitro induction of T-helper cells.

Abstract: MACROPHAGES are of importance in the initiation of immune responses, both in vitro1 and in vivo1,2. Both immune responses involving B cells, such as antibody production3–6, and those involving T cells, such as the lymphocyte transformation7, the mixed lymphocyte reaction (MLR) (refs 8 and 9), and the induction of cytotoxic responses10 require macrophages. Various concepts of macrophage function in immune induction have been suggested. The simplest concept proposed is that macrophages augment lymphocyte survival in vitro11. Although this is one of their functions in vitro, it does not explain fully their role in vitro and especially in vivo. In the induction of antibody responses, two functions were defined, the breakdown of antigens to the appropriate size5 and the presentation of antigen to B cells in an optimally immunogenic manner12. Because the T-cell reactions already studied, such as the MLR, involve ill-defined antigens, the surfaces of living cells, even less is known about the mechanisms of macrophage function in the stimulation of T cells than of B cells.

Cardenolide Storage in Danaus chrysippus (L.) with Additional Notes on D. plexippus (L.)

Abstract: Danaus chrysippus was reared in the laboratory from stock obtained from Kampala (Uganda), Nairobi (Kenya), Dar-es-Salaam (Tanzania) and Freetown (Sierra Leone) and wild-caught samples from Nigeria, southwest Africa and Tanzania were also analysed. D. plexippus was reared on the same plants for comparison. It was found that the adult D. chrysippus is a poor and inconsistent storer of cardiac glycosides compared with D. plexippus, and contained, chiefly, highly polar cardenolides. Populations in East Africa are, on the whole, more efficient storers than those from West Africa, a factor which may contribute to the dearth of mimics in West Africa. Furthermore there appears to be a genetic element in the storage capacity of these butterflies, not merely a 'mirror' effect, depending on the cardenolide content of their food plants. Differences in storage capacity were shown between morphs alcippus from both Sierra Leone and Dar-es-Salaam and aegyptius from Tanzania and Dar-es-Salaam, reared side by side on the same tested food plants. In both cases aegyptius was the better storer but in other broods from Kenya, reared on Asclepias rich in cardenolides, this morph was negative for these substances. During the investigation strains of Asclepias curassavica were found which contained calotropin, but lacked calactin. D. plexippus reared on these plants also lacked calactin, but sequestered and stored it when fed on Gomphocarpus fruticosus which contained both substances. The methods for analysing cardenolides of this type are described. Maps are presented showing the distribution of the three principal morphs of D. chrysippus and the form albinus in Africa.

Sequence of the P R promoter of phage λ

Abstract: The RNA polymerase binding site from the λ PR promoter was isolated and sequenced. This DNA fragment contains the transcription initiation site and shares 25 nucleotides with OR. The sequence preceding the initiation site suggests that the promoter recognition site is not identical with the tight binding and initiation site.

Acidic nonsteroid anti-inflammatory drugs accumulating in inflamed tissue

Abstract: Es wird gezeigt, dass saure Antiphlogistika im entzundeten Gewebe angereichert werden. Alkalische Strukturverwandte zeigen diesen Effekt nicht. Die Bedeutung dieses Befundes fur das Verstandnis der Wirkung bekannter und die Entwicklung neuer nicht steroidaler Antiphlogistika wird diskutiert.

Histamine H2-receptors on single central neurones.

Abstract: THE detection of histamine H2-receptor antagonists1,2 has provided fresh impetus to the investigation of central effects of histamine3–7 and its possible role as a neurotransmitter3,8–10. In the hypothalamus of rat and cat microelectrophoretically applied histamine excites a large number of cells. This action, which is unique to the hypothalamus, is not selectively antagonised by the H1-receptor antagonist mepyramine or by the H2-receptor antagonist metiamide8,9. In the cortex of the cat several H1-antagonists were tested but no specific action could be demonstrated11. We report now on a selective antagonism of metiamide against depressant actions of histamine in the cerebral cortex of cat and rat.

The kinetics of the exchange of G-actin-bound 1: N6-ethenoadenosine 5'-triphosphate with ATP as followed by fluorescence.

Abstract: 1: N6-Ethenoadenosine 5′-triphosphate (ɛATP), a fluorescent analog of ATP, binds to monomeric actin with a binding constant which is only about 5 times smaller than that of ATP. The spectroscopic changes which occur when ɛATP binds to actin are studied and used to monitor the kinetics of nucleotide exchange. The first-order rate constant which is measured at a large excess of ATP over ɛATP strongly depends on the ATP and Ca2+ concentrations. This finding is explained by a mechanism in which the nucleotide dissociates much more easily from Ca2+-free than from Ca2+-bound actin. Of special interest is the temperature dependence of the dissociation rate constant. The Arrhenius plot shows a sharp bend near 24 °C.

The consequences of σ and π conjugative interactions in mono-, di- and triacetylenes. A photoelectron spectroscopic investigation

Abstract: The HeI photoelectron spectra of mono-, di-, and triacetylenes are presented. In these compounds the two-centre π-orbitals of the ethynyl groups conjugate with the π-orbitals of double bonds or benzene moieties, or with the Walsh orbitals of three-membered ring systems. Assuming the validity of Koopmans' approximation, the observed energies of the radical cation states reached by electron ejection from π-orbitals can be rationalized in terms of a simple LCBO-MO model in those cases, where the molecule is planar. The corresponding numerical results for the ionization energies are in excellent agreement with experiment, if the three parameters of the model are properly calibrated. In contrast, the bands assigned to ejection from in plane π-orbitals are shifted to lower energies by ca. 0.5 eV with respect to the expectation values derived from the above model, due to ‘through-bond’ interaction with lower lying σ-orbitals. Extensive σ/π mixing occurs in the non planar compounds for all orbitals. The assignments of the spectra of diethynylmethane, 1,4-hexadiyne, 1,2-diethynylethane and of cis- and trans-diethynylcyclopropane are backed by semiempirical SCF calculations. The spectra of the cis and trans isomers of diethynylethyleneoxide and diethynylethylenesulfide are discussed by comparison with the corresponding hydrocarbons and with oxirane and thiirane respectively. Finally, the following topics are considered in detail: (a) The effect of spin orbit coupling on the spectrum of 1-iodo-1-butyne-3-ene; (b) the effect of the essentially free internal rotation in divinylacetylene on the band shapes of its photoelectron spectrum and (c) the relationship between the conjugative properties of ethylenic π-orbitals and of the Walsh-orbitals of cyclopropane.

Multiple steps in DNA recognition by restriction endonuclease from E. coli K.

Abstract: The process of DNA recognition by the activated form of the restriction endonuclease from E. coli K involves three enzyme-DNA complexes which can be differentiated experimentally. These are: an initial complex formed at a nonspecific site; a recognition complex involving the host specificity site; and a cleavage complex dependent on the presence of ATP.

The Contribution of Computerized Axial Tomography to the Diagnosis of Cerebellar and Pontine Hematomas

Abstract: Case histories are reported of seven patients in whom the diagnosis of cerebellar (four) or pontine hemorrhage (three) was made by computerized axial tomography (CT). In all of the patients except two the diagnosis, established on the basis of a space-occupying high absorption lesion, was proved by either operation or autopsy. In the two remaining cases, the evolution on CT was typical for an intracerebral hematoma, i.e., the high absorption zone was transformed into an area of reduced density. It is concluded that CT is a highly reliable method for the diagnosis and location of posterior fossa hematomas. A CT syndrome, observed in four of the seven cases, is described consisting of a hydrocephalus with the tips of the posterior horns being filled with blood. This seems to be specific for a posterior fossa hematoma having penetrated into the fourth ventricle.

Growth inhibition of animal cells by succinylated concanavalin A

Abstract: A non-agglutinating lectin preparation, succinyl-con A, inhibits the growth of untransformed 3T3 mouse fibroblasts in a manner that mimics density-dependent growth inhibition. The growth inhibitory interaction between succinyl-con A and cells occurs exclusively during the mitotic and/or early G1 phase of the cell cycle.

1,5-Cyclooctadiyne. Preparation and Reactivity

Abstract: 1,5-Cyclooctadiyne 1 was isolated in 2 percent yield from polymerized butatriene 5. Other oligomers of 5 were detected in the reaction mixture by combined GLC./MS. analysis but have not been identified. Diels-Alder adducts of 1 with two equivalents of 1,3-butadiene and of 2,3-dimethyl-1,3-butadiene have been prepared. In the presence of strong base 1 isomerized to cyclooctatetraene. 5 was reformed by photolysis of 1. Attempts to prepare transition metal complexes of 1 failed. Effects of ring strain and of transannular interaction on the reactivity of 1 are discussed. The dimerization of 5 to 1 is predicted to be strongly exothermic.

Follow‐up studies of free gingival grafts

Abstract: Vestibuloplasties with free gingival grafts were performed on 42 teeth in 12 patients exhibiting gingival recession. The tendency toward recurrence was studied after postoperative intervals of 1, 6 and 12 months. The extensions (vestibuloplasties), which were always wider than the transplant, recurred up to the transplantation margin. The transplant itself underwent shrinkage averaging 25 per cent. The vestibular depth, which had been increased by the operation, showed a 25 per cent reduction within 1 month, but then had a tendency to deepen again from 1 to 12 months postoperatively. The marginal free gingiva and sulcus depth were not influenced by the operation.

Effect of chlorhexidine on dental plaque formation under periodontal pack

Abstract: In a first experiment, no appreciable differences in plaque formation under periodontal packs were observed in subjects rinsing with and without 0.2 % chlorhexidine digluconate. In a second experiment, one gram periodontal packs were coaled with 15 to 20 mg of chlorhexidine dihydrochloride powder prior lo application and allowed to remain in situ for 4 days. Significantly less plaque formed under periodontal packs with chlorhexidine powder than with control packs. Chlorhexidine dihydrochloride powder may be recommended under periodontal packs for reduction of microbial plaque.