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Biomedical subjects

W Schulze

Publications and source records attributed to W Schulze.

At least 127 records · Page 7Linked to original sources

Adenylate cyclase and guanylate cyclase activity in the conduction system of rabbit hearts.

In comparison to the working myocytes no remarkable differences in the localization of adenylate cyclase (AC) and guanylate cyclase (GC) were found. The sarcolemmal plasma membrane of the AV node and the Purkinje fibers was the main site of the activity of these two enzymes. GC activity was additionally found at peripheral junctional couplings. Stimulation by hormones and specific activators for both AC and GC was demonstrated with difficulty. The reasons may be more the cytochemical preparation technique than the specificity of the AC and GC in the conducting tissue.

Adenylyl Cyclases↗

Computer-aided three-dimensional reconstructions of the arrangement of primary spermatocytes in human seminiferous tubules.

With the use of a digital image-processing method three-dimensional reconstructions of the arrangement of spermatocytes in human seminiferous tubules were performed. With this method it was possible to investigate the cellular distribution in the tubule in nearly any given perspective and projection. In addition, by means of simple mathematical procedures, such as by transformation of Cartesian coordinates into cylindrical coordinates, it was possible to vary the shape of a reconstruction, i.e., to convert the cylindrical image of a tubular portion into a right-angled r-phi-z-representation. The present work not only confirms the existence of a complex helical plan of organization of the human seminiferous epithelium but also provides further aspects of the phenomenon of physiological germ-cell loss and its integration into the kinetics of spermatogenesis.

Aged↗

Cytochemical localization of adenylate cyclase activity in heart tissue with cerium.

Adenylate cyclase (AC) activity showed a doses depending inactivation of the basal activity and of the sodium fluoride stimulation by cerium in homogenates of unfixed and fixed guinea pig hearts. The isoproterenol and guanine nucleotide stimulation was not more than two times of the basal activity in glutaraldehyde-prefixed heart homogenates in the presence of 2 mmol/l CeCl3. The inactivation of the AC (activity) by cerium was less than in the presence of lead. Test tube experiments showed no differences in the precipitation of imidodiphosphate in comparison with inorganic phosphate. The substrate AMP-PNP was not spontaneously hydrolysed by 2 mmol/l CeCl3. Ultrastructural analysis of cytochemical incubation of glutaraldehyde-fixed slices and small pieces of guinea pig heart tissue showed fine-amorphous precipitations of reaction products localized along the plasma membrane of the sarcolemma, the nexuses of the intercalated discs and the T-tubule membranes. No precipitates were found neither on the junctional nor on other SR membranes. Nonspecific coarse and clumped precipitates have been detected in the intercellular space on components of the basal membranes. It was not able to demonstrate cytochemically stimulation of AC by hormones or by sodium fluoride. The localization of the basal AC activity in heart tissue seems to be better with cerium as capture agent than with lead. However, differences in the localization of the AC activity in heart tissue were not observed.

Adenylyl Cyclases↗

Cyclic AMP metabolism and interferon induction in mice after treatment with 10-carboxymethyl-9-acridanone.

The low molecular weight substance 10-carboxymethyl-9-acridanone (CMA) is capable to induce interferon (IFN) production. In order to determine the effect of CMA on cyclic AMP alterations in relation to IFN production, male ABD2F1 hybrid mice were orally treated with several concentrations of CMA (400, 600 and 800 mg/kg) for varying periods of time up to 24 hr. IFN titres were detected as early as 3 and 4 hr, respectively, in mouse plasma after CMA administration, and their production continued for at least 24 hr. Maximum IFN titres were assayed in the presence of 800 mg/kg (3,200 IU/ml) CMA. Measuring of the intracellular concentrations of cyclic AMP in thymus and spleen revealed that in early stage (0.5 to 2 hr) CMA exhibited a dose dependent increase. The drug acted as an inhibitor of low Km cAMP phosphodiesterase in cell homogenates; a significantly enhanced enzyme activity (1 to 4 hr) was found after exposure to CMA in vivo.

3',5'-Cyclic-AMP Phosphodiesterases↗

Adrenergic regulation of the acute ischaemic myocardium: facts, interpretations and consequences.

Anoxic stress is accompanied by activation of the central and peripheral sympathetic nervous system resulting in a high local catecholamine concentration. The authors studied how myocardial cells cope with the high level of catecholamines under ischaemic conditions. The beta-adrenoceptor-adenylate cyclase system (AC) was investigated in different models of ischaemia and anoxia (global ischaemia, low-perfused hearts, coronary artery ligation) in rat hearts. It was shown that beta-receptor function is not changed up to 40 min of ischaemia. Myocardial AC function was depressed in the total ischaemic myocardium but not in the low-perfused hearts indicating a non-uniform alteration of AC function. Reduced AC activity was completely reversible by aerobic perfusion as long as the ischaemic period did not exceed 20 min. Depression of AC function during severe ischaemia was avoided by reducing Ca2+ in the extracellular fluid and by pretreatment with Ca2+ channel blockers (verapamil). Depression of AC function during severe ischaemia is caused mainly by increased intracellular Ca2+ which inhibits AC at its catalytic site. Myocardial ischaemia alters the response of myocardial cells to catecholamines and other activators of the AC system. This alteration is time-limited and turns damage to AC function from reversible to irreversible after prolongation of ischaemia to more than 30 min.

Adenylyl Cyclases↗

[The synthesis and biologic activity of analogs of 1,4-benzoquinone-guanylhydrazone-thiosemicarbazone. 2. Substitution at the quinone ring by alkyl groups].

Because of the anticancer activity of 1,4-benzoquinone-guanylhydrazone-thiosemicarbazone (1a) some analogues were synthesized, containing alkyl groups at the quinone moiety. If necessary, the structure of the obtained compounds was confirmed by 1H-NMR-spectroscopy. The anticancer and the antibacterial activities were investigated. The guanylhydrazone-thiosemicarbazones of tolu-,p-xylo-and thymo-quinone showed much lower activities not only against the murine leukemias L 1210 and P 388, but also against Bacillus subtilis ATCC 6633. No correlation could be found between the biological activity and the redox potential.

Animals↗

[Classification of the germinal epithelium in Java monkeys (Macaca cynomolgus) using digital image processing].

Testicular tissue of two adult crab-eating macaques was used to investigate the distribution of the spermatids in the seminiferous tubules. For this purpose, morphological criteria for distinction among the various degrees of development of these cells were elaborated. Subsequently, based upon analyses of serial sections, three-dimensional reconstructions of the cellular distribution pattern were generated by means of digital image processing. In these reconstructions it became evident that the spatial extension of a single differentiation stage can vary considerably. Large tubular portions that contained a single differentiation stage alternated with those exhibiting several differentiation stages which occupied only small patch-like areas of the seminiferous epithelium. Particularly in the latter portions of the tubule a helical continuity of subsequent stages in the sense of a wave of spermatogenesis became immediately obvious. Transitory changes in the direction of the wave (modulations) occurred frequently. The present findings support the suggestion that an uniform kinetic principle of mammalian spermatogenesis exists, which is subjected to slight modifications during the evolution of primates.

Animals↗

The ultrastructure of sensory nerve endings in the human knee joint capsule.

The ultrastructure of sensory nerve endings in the human knee joint capsule was studied. Three types of nerve endings were found: free nerve endings (FNE), Ruffini corpuscles and Pacini corpuscles. In the joint capsule, FNE are located below the synovial layer and within the fibrous layer near blood vessels. These nerve terminals derive from myelinated A delta-fibres or from unmyelinated C-fibres. Their structure is almost identical to FNE in human hairy and non-hairy skin. Ruffini corpuscles are present within the fibrous layer and the ligaments of the capsule in three variations: small Ruffini corpuscles without a capsule, small with a connective tissue capsule, and large Ruffini corpuscles with an incomplete perineural capsule. Their afferent axons are myelinated and measure 3-5 micron in diameter. Inside the corpuscle, nerve terminals are anchored in the connective tissue belonging to the fibrous layer or to the ligaments respectively. The presence of an incomplete perineural capsule depends on the structure of the surrounding connective tissue. In ligaments with collagenous fibrils oriented in a parallel fashion, the perineural capsule is well-developed and the Ruffini corpuscle resembles a Golgi tendon organ; in areas where the fibrils show no predominant orientation, Ruffini corpuscles lack a capsule. Small Pacini corpuscles are situated within the fibrous layer near the capsular insertion at the meniscus articularis or at the periost. They consist of one or several inner cores and a perineural capsule of 1-2 layers. Larger Pacini corpuscles with one or several inner cores and a perineural capsule consisting of 20-30 layers are found on the outer surface of the fibrous layer. The ultrastructure of these nerve endings is compared with the ultrastructure of articular receptors of various animals and with the ultrastructure of sensory nerve endings in the skin of several mammalian species including man.

Adult↗

Reversible inhibition of adenylate cyclase activity in the ischemic myocardium.

Adenylate cyclase (AC) function was studied in homogenate and particulate preparations of ischemic rat heart obtained from three models: anoxic-ischemic incubations, coronary artery ligation, and global low-flow perfusion of isolated hearts. Both basal activity and the function of AC measured in the presence of NaF (8 X 10(-3)M), Gpp(NH)p (10(-5)M), and L-(-)-isoprenaline (10(-8)-10(-4)M) were reduced to 50% of the control value in homogenates of hearts incubated under anoxic-ischemic conditions for 10 min. Comparable results were obtained with homogenates from the ischemic area 20 min after coronary artery ligation in anesthetized open-chest rats with artificial ventilation. Reduced AC activity of the anoxic-ischemic hearts was completely reversible by aerobic reperfusion, provided the ischemic period did not exceed 20 min. AC activity in homogenates of isolated hearts perfused at low-flow was not changed, indicating a nonuniform alteration of AC system in nonperfused and low-flow perfused areas of the ischemic heart. Depression of myocardial AC function during severe ischemia was avoided by reducing Ca2+ in the incubation buffer, in combination with addition of EGTA during the homogenization step, and by pretreating the animals with verapamil. It is suggested that the depressed AC function is caused mainly by an increase in intracellular Ca2+, which inhibits the enzyme at its catalytic site. A negative feedback control of AC function by Ca2+ is postulated that may operate especially in the ischemic myocardium.

Adenylyl Cyclases↗

[Synthesis and biological activity of 1,4-benzoquinone-guanylhydrazone-thiosemicarbazone analogs. 1. Substitution at the S atom].

The synthesis of S-substituted derivatives of 1,4-benzoquinone-guanylhydrazone-thiosemicarbazone is described. The obtained 1,4-benzoquinone-guanylhydrazone-S-alkyl (resp. aralkyl)-isothiosemicarbazones, in comparison with the unsubstituted standard compound, showed a significantly decreased biological activity against the murine leukemias L 1210 and P 388 as well as against the growth of several kinds of bacteria. Therefore the S-substitution seems not to be useful for reaching a maximum activity.

Animals↗

Interaction of DNA with tilorone derivatives: viscometric investigations.

Interaction of DNA with tilorone and six of its derivatives was studied in solution. This was done by viscosity measurements on both low and high molecular weight calf thymus DNA, in order to interpret the experimental results in terms of changes of DNA contour length (intercalation) and of persistence length (stiffening and bending). Qualitative and semiquantitative analysis delivered the following results: The carbonyl derivatives of tilorone bind more strongly to DNA than tilorone itself. The ligands with their two positively charged terminal groups favour DNA-DNA association. All carbonyl derivatives studied intercalate completely whereas the compound with quaternary nitrogens does not. No significant DNA stiffening effects were observed (contrary to the interaction of DNA with anthracycline derivatives) indicating the absence of a strong multipoint clamping between ligand and helix in relatively great distance. Different ligands induce different helix bending effects. The magnitude of the helix bending angle probably depends on the DNA base sequence. For some derivatives this angle is different at low and high ratio vt of added ligand molecules per DNA phosphate. This novel observation suggests the existence of heterogeneous, i.e. specific, binding as also found for tilorone by other authors on the basis of spectroscopic measurements using synthetic polynucleotides.

Animals↗