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Biomedical subjects

R Rudolph

Publications and source records attributed to R Rudolph.

At least 145 records · Page 8Linked to original sources

Neuronal ceroidosis (ceroid-lipofuscinosis) in a Blue Heeler dog.

Neuronal ceroidosis was observed in an 18-month-old male Blue Heeler dog which was euthanized after showing a progressive gait and behavior abnormality, depression, paresthesia, and vision deterioration. The brain was slightly atrophic. Histopathology revealed autofluorescent, periodic acid-Schiff, luxol fast blue, and oil red O-positive intracytoplasmic granules in the neurons of the brain and spinal cord. There was a moderate diffuse reduction in the number of cerebellar and cerebrocortical neurons. Ultrastructurally, these neuronal cytosomes were diverse with preponderance of membranous profiles and granular matrix.

Animals↗

Isoproterenol inhibition of horse serum cholinesterase is connected with subunit dissociation.

Tetrameric cholinesterase from horse serum undergoes concentration-dependent dissociation. The dimer is highly stable so that even on SDS polyacrylamide gels subunit dissociation to the 80-kDa polypeptide chains is incomplete. Glutaraldehyde cross-linking confirms this finding, giving rise to a tetramer: dimer ratio of approximately 1:1. The beta-adrenergic agent isoproterenol acts as an inhibitor of the enzyme with respect to butyrylthiocholine hydrolysis; inhibition kinetics point to a dissociative effect of the ligand as the underlying mechanism (Söylemez, Z. & Ozer, I. (1985) Comp. Biochem. Physiol. 81c, 433-437). Evidence from sedimentation analysis confirms this hypothetical mechanism: the sedimentation coefficient in the presence of saturating concentrations of both the substrate butyrylthiocholine and the inhibitor isoproterenol shows a 35 +/- 5% decrease; in high speed sedimentation equilibria the weight average molecular mass is shifted from the tetramer (Mr = 312 +/- 12 kDa) to the dimer (Mr = 160 +/- 10 kDa). The transition is complete at isoproterenol concentrations below saturation. Applying glutaraldehyde cross-linking to monitor the particle distribution at varying isoproterenol concentrations confirms the change in quaternary structure in a qualitative way. Enzyme concentrations applied in the present experiments are in the range of the concentration of cholinesterase in horse serum. Therefore the dissociative mechanism of isoproterenol on the enzyme may be of biological significance.

Animals↗

Cultured myofibroblasts: a useful model to study wound contraction and pathological contracture.

From both human and animal tissues, myofibroblasts can be successfully cultured in vitro through multiple passages. As compared with cultured fibroblasts from control tissues, early passage myofibroblasts have slower growth cycles, as is typical of highly differentiated cells. Also in early passage, differences between myofibroblasts and fibroblasts in tissue culture in vivo can be preserved. Late passage animal studies suggest dedifferentiation in both morphology and growth cycle rate. As indicated by our data, which have been discussed in detail in our previous investigations, we believe that further studies may help to define how such dedifferentiation occurs and may determine ways to do so clinically. However, such control attempts must take into account the heterogeneity of myofibroblast and fibroblast populations which these studies have identified.

Adenocarcinoma↗

Aesthetic aspects of composite oromandibular cancer resection and reconstruction.

Disfigurement after oromandibular cancer surgery is as much feared as the tumor itself. A deviated jaw, collapsed neck and muffled speech are external markers that may prevent normal life. Yet such stigmata are not necessary. For two years we have used an immediate reconstruction that avoids these problems. In 12 patients we used a pectoralis musculocutaneous flap plus a stainless steel shaped bridging bone plate placed under or through the flap. The flap reconstructs the floor of the mouth, while the bridging bone plate preserves mandibular continuity. A McFee incision avoids vertical scarring, and the muscle pedicle duplicates the missing neck contents. Meticulous lip closure completes the procedure, which often does not necessitate tracheotomy scarring. Our patients have maintained a highly satisfactory appearance of face and jaw, with normal swallowing and clear speech. In treatment of oromandibular cancer, aesthetic considerations are essential.

Carcinoma, Squamous Cell↗

Mechanism and specificity of reconstitution of dimeric lactate dehydrogenase from Limulus polyphemus.

D-Lactate dehydrogenase (EC 1.1.1.28) from Limulus polyphemus is a homodimer which is composed of identical subunits of Mr = 35 000. The enzyme may be reversibly denatured and dissociated at acid pH or in 6M guanidine X HCl. The sigmoidal time course of reactivation obeys a consecutive uni-bimolecular mechanism with k1 = 6 X 10(-4) S-1 and k2 = 1.3 X 10(-4) M-1 S-1 (20 degrees C) as first- and second-order rate constants. Cross-linking experiments with glutaraldehyde prove that reactivation and dimer formation run parallel. Joint "synchronous" reconstitution of the enzyme with dimeric porcine mitochondrial malate dehydrogenase (after denaturation in 6M guanidine X HCl) does not yield active hybrids. The unchanged kinetics of reactivation in the absence and presence of the prospective partner of hybridization prove that inactive hybrid intermediates may also be excluded. The absence of hybrids upon synchronous reconstitution of the two closely related dimeric NAD-dependent dehydrogenases clearly suggests that the assembly of nascent oligomeric proteins must be highly specific.

Animals↗

Isolation, physicochemical properties, and folding of octopine dehydrogenase from Pecten jacobaeus.

Two types (isoenzymes) of octopine dehydrogenase (A and B) from Pecten jacobaeus adductor muscle were purified to homogeneity, applying affinity chromatography as an efficient final step of purification. Both forms of the enzyme differ in their electrophoretic mobility. All other physico-chemical and enzymatic properties, as well as the folding behaviour were found to be identical. Interconversion of one form into the other was not detectable. Sedimentation equilibrium, gel permeation chromatography, and NaDodSO4/polyacrylamide gel electrophoresis yield a relative molecular mass of 45000 +/- 1500 for both native and denatured enzyme. The unfolding transition at varying guanidine X HCl concentrations is characterized by a two-step profile: at 0.4-0.8 M, partial unfolding is parallelled by inactivation; at 2.0-2.4 M the residual structure is destroyed in a second unfolding step. Beyond 2.8 M no further changes in fluorescence emission and dichroic absorption are observed. At 0.4-1.8 M guanidine X HCl, partial unfolding is superimposed by aggregation. The emission maximum of the intrinsic protein fluorescence at 327 nm is shifted to 352 nm upon denaturation in 6 M guanidine X HCl. Changes in the far-ultraviolet circular dichroism indicate complete loss of the overall backbone structure in this denaturant, including the native helix content of about 33%. Denaturation in 6 M guanidine X HCl, as monitored by the decrease of protein fluorescence, is fast (less than 8s). Upon reactivation after short denaturation, about 25% of the activity is recovered in a fast initial phase (less than 20s). The product of this phase has a similar stability towards destabilizing additives or proteases as the native enzyme. The slow phase of reactivation, which predominates after long-term denaturation, is determined by a single first-order reaction characterized by tau = 29 +/- 3 min (20 degrees C). This reaction must be a relatively late event on the folding pathway, preceded by the fast formation of a structured intermediate, as indicated by the immediate recovery of the native fluorescence. The structural rearrangements, which are rate-limiting for reactivation after long-term denaturation, are characterized by a high energy of activation (112 +/- 8 kJ/mol). The slow reactivation step is compatible in rate with the first-order folding reactions involved in the reconstitution of several oligomeric dehydrogenases [c.f. R. Jaenicke and R. Rudolph (1983) Colloq. Ges. Biol. Chem. Mosbach 34, 62-90].

Amino Acid Oxidoreductases↗

[Therapeutic value of antihistamines today. Dermatoses and allergic diseases of the mucous membranes].

Factors to consider while administering antihistaminic agents: The dosage and time of administration should be related to the expected histamine release or the histamine release which has already taken place. The antihistaminic agents selected for treatment must take a) the type of receptor that is to be blocked (H1, H2), and b) additional pharmacologic properties such as sedation into account. H1-antagonists can be used to treat symptoms of various forms of acute and chronic urticaria, including physical urticaria, cholinergic urticaria and allergic rhinitis. Their indication for allergic forms of bronchial asthma has limitations. Antihistamines suppress the starter function of histamines and therefore, the development of further mediators. Furthermore, they influence the role of histamines in physiologic neurotransmitter processes. The combination of H1- and H2-antagonists can be beneficial in certain cases. Topical application of H1-antagonists leads to an anaesthetising , antipruritic effect and limits vessel permeability. The effect is noticeable after approximately 30 minutes. It is of therapeutical use if applied prior to histamine release.

Administration, Oral↗

Dupuytren's disease: comparative growth dynamics and morphology between cultured myofibroblasts (nodule) and fibroblasts (cord).

The excised palmar fascia of 11 patients with Dupuytren's disease was separated clinically into nodules and cords. Myofibroblasts were seen by light and electron microscopy in each of the nodules, but the cords generally lacked myofibroblasts. Only one cord specimen had microscopic features that were intermediate between nodule and cord. Electron microscopy demonstrated that in vivo differences between myofibroblasts from nodules and fibroblasts from cords and control skin samples could be preserved in vitro. Growth studies showed slower growth of cultured myofibroblasts (mean +/- SD generation time 68.7 +/- 15 h) than cord-derived fibroblasts (mean +/- SD generation time 51.5 +/- 0.9 h). These data suggest that the life cycle of the myofibroblasts from Dupuytren's disease nodules differs from that of fibroblasts found in cordlike tissues. These myofibroblasts have biological characteristics nearly identical to those of myofibroblasts found in other contracting tissues, such as granulating wounds and breast cancer.

Biopsy↗

The effect of delay on flap survival in an irradiated field.

Chronic radiation skin injury without ulceration was induced in rats by administering either 3000 or 5000 rads in staged doses. Either 4 or 8 months later, McFarlane et al. dorsal flaps were elevated, with half being delayed and half non-delayed. Measurements showed that flap survival in irradiated skin was significantly increased by delay [approximately two of four experimental groups (4 months, 5000 rads; and 8 months, 3000 rads)]; flap survival was increased with borderline significance in a third experimental group (8 months, 5000 rads). These data indicate that flap survival can be increased by delay in an irradiated field. The presence of the vascular delay phenomenon suggests that microvascular occlusion alone cannot account for radiation-induced complications in skin.

Animals↗