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Biomedical subjects

C Schulze

Publications and source records attributed to C Schulze.

At least 73 records · Page 4Linked to original sources

[Spinal ataxia caused by an occipito-atlanto-axial malformation in a lamb].

A three month old lamb suffering from locomotory disturbances was submitted to the clinic. It had a tilted head to the left and an atactic gait especially in the hind limbs. When it was forced to stop or to change direction it fell down. General condition and sensorium were apart from a reduced bathyaesthesia normal. By clinical and laboratory examination some possible causes of locomotion disturbances in lambs like copper deficiency, nutritive muscle dystrophy and meningitis could be ruled out. By X-ray examination an asymmetry of the os occipitale and atlas was diagnosed. They were not well distinguishable from each other. The second vertebra showed a rotation with angulation of its longitudinal axis to the left and a dorso-lateral subluxation. By myelography a narrowing of the vertebral canal between first and second vertebra could be shown. Because of the poor prognosis the animal was euthanised. The pathological examination confirmed and completed the X-ray findings.

Animals↗

[Quantitative CT assessment of the proximal femur. Experimental studies on its correlation with breaking load in femoral neck fractures].

PURPOSE: In an experimental study, the correlation between the trabecular bone density of the different regions of the proximal femur and the fracture load in the setting of femoral neck fractures was examined. METHODS: The bone mineral density of 41 random proximal human femora was estimated by single-energy quantitative CT (SE-QCT). The trabecular bone density was measured at the greatest possible extracortical volume at midcapital, midneck and intertrochanteric level and in the 1 cm3 volumes of the centres of these regions in a standardised 10 mm thick slice in the middle of the femoral neck axis (in mg/ml Ca-hydroxyl apatite). The proximal femora were then isolated and mounted on a compression/bending device under two-legged stand conditions and loaded up to the point when a femoral neck fracture occurred. RESULTS: Statistical analysis revealed a linear correlation between the trabecular bone density and the fracture load for the greater regions, with the highest value in the maximal area of the head (coefficient factor r = 0.76). CONCLUSION: According to our data, the measurement of the trabecular bone by SE-QCT at the femoral head is a more confident adjunct than the neck or trochanteric area to predict a femoral neck fracture.

Adult↗

Photoaffinity labeling of the head-activator receptor from hydra.

A photoaffinity ligand for the head-activator (HA) receptor from hydra was synthesized using solid-phase peptide synthesis and coupling of two HA peptides over their epsilon-amino groups of Lys7 with succinimidyl esters. The new ligand, Bpa-HA-HA bipeptide, contains one normal HA peptide and another where p-benzoylphenylalanine (Bpa) was added at the amino terminus to allow ultraviolet activation and Tyr11 instead of Phe11 for radioiodination. The 125I-Bpa-HA-HA bipeptide bound with nanomolar affinity to the HA receptor from the multiheaded mutant of Chlorohydra viridissima as measured in a filter assay. After photoaffinity labeling of the hydra membrane fraction, a 200-kDa band was detected using reducing or non-reducing SDS/PAGE and autoradiography. Unlabeled HA derivatives, but no other neuropeptides, inhibited the labeling. Competition experiments with HA-HA homobipeptide in the nanomolar range indicate that predominantly the low-affinity and not the high-affinity HA receptor was photolabeled. Further evidence that the labeled molecule is the HA receptor comes from specific photoaffinity labeling with a second ultraviolet-activatable ligand containing p-nitrophenylalanine. The HA receptor could be functionally solubilized with Triton X-100 or Chaps. In the solubilizate the 200-kDa HA receptor was photolabeled specifically by both ligands. Liquid-phase isoelectric focussing of the solubilizate indicated a pI of about 5.4 of the photolabeled molecule. After chemical deglycosylation with trifluoromethanesulfonic acid, the apparent molecular mass of the labeled molecule was decreased to 180 kDa, indicating that the receptor is glycosylated.

Affinity Labels↗

Impact of different classes antimicrobial agents on plasma endotoxin activity.

OBJECTIVE: To investigate the influence of different classes and doses of antibiotics on endotoxin release in gram-negative infection in a rat model of intra- abdominal infection. DESIGN: Immediately after intraperitoneal inoculation of Escherichia coli (5 x 10(7) colony-forming units/kg), anesthetized Wistar rats were treated with a single intravenous dose of an antimicrobial agent: cefotaxime (40 mg/kg), ciprofloxacin (3 mg/kg or 6 mg/kg), imipenem (7 mg/kg or 14 mg/kg), or gentamicin (5 mg/kg). An untreated control group received 0.9% sodium chloride instead of antibiotic. Plasma endotoxin activity, blood bacteria count, and mean arterial pressure were monitored at 60-minute intervals for 5 hours. At the end of the experiment, lavage was performed to determine the bacteria count in the peritoneal cavity. RESULTS: In the untreated group, the blood bacteria count increased rapidly. Five hours after therapy, the plasma endotoxin activity in the cefotaxime group was higher by a factor of 3.6 than in the untreated group. Compared with the cefotaxime group, endotoxin activity was approximately 26% lower in the ciprofloxacin (3 mg/kg) group, 35% lower in the imipenem groups, and 38% lower in the gentamicin group. The lowest endotoxin levels were in the high-dose ciprofloxacin group. Bacteria counts in the peritoneal cavity were lowest in the gentamicin and high-dose ciprofloxacin groups. Except in the high-dose ciprofloxacin group, the endotoxin increase in the therapy groups was associated with a significant (P < .05) decrease in mean arterial pressure. CONCLUSIONS: In the early phase of therapy, antibiotic-induced endotoxin release is influenced by the mode of action of the agent class. This is not the sole influence in every class. With quinolones, this effect is also influenced considerably by dosage, ie, by pharmacodynamics.

Animals↗

Characterization of the major DNA adduct formed by the food mutagen 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAalphaC) in primary rat hepatocytes.

Cooking of proteinous food results in the formation of heterocyclic amines. Among these, 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAalphaC) has been identified as a mutagenic pyrolysis product of soya protein and has been detected in grilled or pan fried meat. It was subsequently proven to be carcinogenic in mice and, recently, in rats and to form covalent DNA adducts in vitro and in vivo. The corresponding nitro compound, 2-nitro-3-methyl-9H-pyrido[2,3-b]indole (MeNalphaC), was prepared and shown to be a direct acting mutagen in the Ames Salmonella reversion assay. When MeNalphaC was chemically reduced in the presence of DNA a major DNA adduct was detected using the 32P-postlabelling assay. This major adduct was characterized by UV spectroscopy and mass spectrometry as N-(deoxyguanosin-8-yl)-2-amino-3-methyl-9H-pyrido[2,3-b]indole. This structure was corroborated by identification of the modified base as a guanine moiety modified at the C8 position as judged by chromatographic and spectral comparison with a standard synthesized from acetylated guanine-N3-oxide and MeAalphaC was characterized by UV/Vis and 1H NMR spectroscopy and mass spectrometry. Treatment of primary rat hepatocytes with MeAalphaC (100 microM, 24 h) resulted in adduct levels of 9.8 fmol/microg DNA as determined by 32P-postlabelling analysis. Using HPLC analysis, two major 32P-labelled adducts were observed accounting for 80 and 13% of total binding respectively. The major adduct was chromatographically indistinguishable from the synthetic deoxyguanosine-C8 adduct using both ion-exchange thin layer or reversed-phase HPLC. Although MeAalphaC is formed only in low p.p.b. levels in cooked food, the contribution to the human carcinogenic risk that might be imposed by heterocyclic amines is not to be neglected.

Animals↗

Fixed-exit monochromators for high-energy synchrotron radiation.

Current developments in X-ray optics for synchrotron radiation beamlines are briefly reviewed. Reference is made to recent work on adaptive mirrors, cryogenic cooling of monochromators, use of thin diamond crystals, and active correction of the crystal shape for distortions caused by beam heating. The use of bent Si crystals as monochromators is discussed in detail. At high energies Si crystals become transparent to X-rays allowing new monochromator constructions. Bending of the crystal increases the energy bandpass and allows focusing. Different combinations of bent crystals that provide a fixed exit beam are discussed. These include vertically diffracting meridionally focusing Laue-Laue crystals, a Laue crystal combined with a sagittally focusing Bragg crystal, and a Laue-Bragg pair of crystals which provides meridional focusing at two stages.

Journal Article↗

p120, a p120-related protein (p100), and the cadherin/catenin complex.

Cadherins and catenins play an important role in cell-cell adhesion. Two of the catenins, beta and gamma, are members of a group of proteins that contains a repeating amino acid motif originally described for the Drosophila segment polarity gene armadillo. Another member of this group is a 120-kD protein termed p120, originally identified as a substrate of the tyrosine kinase pp60src. In this paper, we show that endothelial and epithelial cells express p120 and p100, a 100-kD, p120-related protein. Peptide sequencing of p100 establishes it as highly related to p120. p120 and p100 both appear associated with the cadherin/catenin complex, but independent p120/catenin and p100/catenin complexes can be isolated. This association is shown by coimmunoprecipitation of cadherins and catenins with an anti-p120/p100 antibody, and of p120/p100 with cadherin or catenin antibodies. Immunocytochemical analysis with a p120-specific antibody reveals junctional colocalization of p120 and beta-catenin in epithelial cells. Catenins and p120/p100 also colocalize in endothelial and epithelial cells in culture and in tissue sections. The cellular content of p120/p100 and beta-catenin is similar in MDCK cells, but only approximately 20% of the p120/p100 pool associates with the cadherin/catenin complex. Our data provide further evidence for interactions among the different arm proteins and suggest that p120/p100 may participate in regulating the function of cadherins and, thereby, other processes influenced by cell-cell adhesion.

Amino Acid Sequence↗

Relation between myocardial beta-adrenoceptor density and hemodynamic and neurohumoral changes in a rat model of chronic myocardial infarction: effects of ibopamine and captopril.

OBJECTIVES: The purpose of this study was to investigate the changes in beta-adrenoceptor density (Bmax) and distribution in a model of chronic myocardial infarction in rats, and to relate possible changes to hemodynamic and neurohumoral abnormalities. In addition, we examined the effects of 8 weeks treatment with ibopamine and captopril. METHODS: There were 3 experiments: (1) Bmax and plasma catecholamines were examined (n = 46), (2) Bmax was compared in infarcted and non-infarcted tissue (n = 13), and (3) contractile function was evaluated by isolated heart perfusion (n = 40). Of rats in Expts. (1) and (3), 50% had myocardial infarction induced by coronary ligation and 50% were controls. Each group was divided between ibopamine, ibopamine and captopril, or standard (no drug) treatment. RESULTS: Bmax was not decreased in rats with myocardial infarction (10.8 +/- 0.8 fmol/mg protein), compared to normal rats (11.4 +/- 0.6 fmol/mg protein), and the ratio beta 1/beta 2 was also unaffected. In infarcted tissue, Bmax was significantly (P = 0.03) lower than in non-infarcted tissue. Baseline left ventricular pressure, systolic and diastolic dP/dT were all impaired (P < 0.001), and plasma norepinephrine levels were elevated in rats with myocardial infarction (16.03 +/- 230 vs. 1287 +/- 83 pg/ml; P < 0.05), compared to normals. Both ibopamine alone and in combination with captopril reduced the elevated plasma norepinephrine levels in infarcted rats (P < 0.001), but only the combination of the 2 drugs significantly increased Bmax in infarcted rats (14.7 +/- 0.8 fmol/mg protein; P = 0.03 vs. untreated myocardial infarction), while ibopamine alone had no significant effect (13.1 +/- 1.1 fmol/mg protein; p = ns). Also, active drug treatment had no significant effect on the hemodynamic changes. CONCLUSIONS: In this coronary artery ligation model of myocardial infarction in rats, no beta-adrenoceptor down-regulation is observed, despite marked abnormalities in baseline left ventricular function and plasma norepinephrine levels. The combination of ibopamine and captopril significantly increases Bmax in infarcted rats, which is accompanied by a reduction in plasma norepinephrine levels, but not by an improvement in hemodynamic parameters.

Adrenergic beta-Agonists↗

Digital optical card. A promising technology for documentation and communication of images.

PURPOSE: To assess a patient-oriented digital optical card (OC) for documentation and communication of images using the analysis of breast microcalcifications to illustrate its resolution power. METHODS: Fifty film mammograms with histologically proved clustered microcalcifications were digitized using a 5 lp/mm CCD-scanner. A region of interest containing the cluster was selected for documentation on an OC as an overview OC-image and as a magnified OC-image (5 lp/mm). The shape (spherical/nonspherical) as well as the total number of microcalcifications were quantitatively analyzed by 2 radiologists. RESULTS: The detection rate for total number of overall and spherical microcalcifications using digital media was significantly reduced (p < 0.01) compared to analog mammography. There were no significant differences in the detection rate of nonspherical microcalcifications between film mammograms (100%) and magnified section OC-images (92.7%). The overview OC-image revealed 72% of those calcifications (p < 0.01). CONCLUSION: According to our results, this technology is not appropriate for diagnosis of breast microcalcifications, but may be a promising communication digital medium for transmitting an image/report unit to referring physicians.

Breast Neoplasms↗

Junctions between pericytes and the endothelium in rat myocardial capillaries: a morphometric and immunogold study.

Pericytes are cells of mesodermal origin which are closely associated with the microvasculature. Despite numerous studies little is known about their function. We have studied the relationship between pericytes and the endothelium in rat myocardial capillaries employing ultrastructural and immunogold techniques. 14% of the subendothelial cell membrane is covered by comparatively small pericytic cell processes. About half of these processes are completely embedded in basement membrane material, whereas the remaining half forms closer contacts with the endothelium. These contacts are devoid of anti-laminin immunogold label, a marker for basement membranes. A small fraction of these contacts has been identified as tight junctions resembling those seen between endothelial cells in capillaries of the same tissue. The remaining majority of junctions reveals a cleft of approximately 18 nm between the apposed membranes in which a succession of cleft-spanning structures can often be detected. It was also found that pericytic processes are preferentially located close to interendothelial junctions. We suggest that the high frequency of intimate junctions between pericytes and the endothelium and the preferential localisation near paracellular clefts may have functional significance.

Animals↗

The sensory innervation of the gingiva and mucosa in Monodelphis domestica: an ultrastructural study.

The location and structure of sensory nerve endings was examined in the mucosa and in the gingiva propria adjacent to the third premolar of Monodelphis domestica by light and electron microscopy. The mucous membrane of the gingiva propria is covered with a stratified keratinized squamous epithelium. The mucous membrane of the adjacent inner aspect of the lip and of the vestibulum oris were covered with a nonkeratinized squamous epithelium. Free nerve endings, Merkel nerve endings and lamellated corpuscles were found in all the examined areas. Free nerve endings were located in the connective tissue papillae between the epithelial cones, in the basal layer of the epithelium and directly under the epithelium of the cones. They were innervated by myelinated A-delta- and nonmyelinated C-fibers. The basal layer of the first three to four epithelial cones of the gingiva propria contained single or groups of Merkel nerve endings. The epithelial cones of the oral mucous membrane contained five times more Merkel nerve endings than those of the vestibular mucous membrane. Lamellated corpuscles were mainly found in the plica sublingualis. In the connective tissue below the epithelial cones of the mucous membranes they usually occur with a perineural capsule, in the connective tissue papillae between the cones they occur without a perineural capsule. In the latter position they resemble the Meissner corpuscles of glabrous skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The sensory innervation of the periodontium of the third premolar in Monodelphis domestica.

Location and structure of sensory nerve endings in the periodontium of the third premolar in Monodelphis domestica have been investigated by means of light and electron microscopy. The periodontal cleft of the tooth is apically enlarged. The number of nerve endings increases towards apex. Three types of sensory nerve endings have been observed: free nerve endings, Ruffini nerve endings and lamellated corpuscles. Free nerve endings could only be identified by electron microscopy. Ruffini nerve endings are only incompletely surrounded by lamellae of the terminal Schwann cell. Protrusions of nerve terminals of the Ruffini corpuscles are anchored between bundles of collagen fibers. Small lamellated corpuscles occur exclusively in the apical portion of the periodontium. Ruffini and lamellated corpuscles are considered as part of a masticatory reflex feedback control system. Ruffini corpuscles detect tension, rapidly adapting lamellated corpuscles detect pressure and vibration in the periodontium. Free nerve endings may function as thermoreceptor or nociceptor.

Animals↗

Immunohistochemical localization of adherens junction components in blood-brain barrier microvessels of the rat.

The morphology and molecular composition of intercellular adherens junctions have most frequently been described in epithelial cells and the fascia adhaerens of the intercalated disc. A group of cytoplasmic molecules is known to be associated with adherens junctions. The intercellular bond is mediated by cadherins which bridge the cells by homophilic binding. Recently, endothelial cells have also been shown to form intercellular junctions of the adherens-type. However, they are morphologically less distinct and little is known about their molecular components. In this study we report the localization of some adherens junction components in intact microvessels of the blood-brain barrier in the rat. We used antibodies raised against alpha-actinin, vinculin, zyxin, cadherin (antipan-cadherin antibody) and A-CAM (N-cadherin) in immunohistochemical experiments at light and electron microscopical levels. Microvessel walls reacted positively for all antigens throughout postnatal development. All antigens were localised, though not necessarily exclusively, to interendothelial junctions. At the ultrastructural level, pan-cadherin reactivity was present throughout the entire length of the cleft. These results could mean that in blood-brain barrier endothelial cells the complex tight junction is embedded in an adherens junction which occupies the entire length of the cleft.

Animals↗

Rat insulin-degrading enzyme: cleavage pattern of the natriuretic peptide hormones ANP, BNP, and CNP revealed by HPLC and mass spectrometry.

The degradation of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) by insulin-degrading enzyme (IDE) has been investigated. As revealed by high-performance liquid chromatography, all three peptides are sequentially cleaved at a limited number of sites, the latter of which were identified by mass spectrometric analyses. The studies revealed that ANP is preferred as substrate over BNP and CNP. ANP degradation is rapidly initiated by hydrolysis at the Ser25-Phe26 bond. Three additional cleavage sites were identified in ANP after prolonged incubation with IDE; in contrast, three and two bonds were hydrolyzed in BNP and CNP, respectively. Analysis of the nine cleavage sites shows a preference for basic or hydrophobic amino acid residues on the carboxyl side of a cleaved peptide bond. In contrast to most of the peptide fragments generated by IDE activity, the initial ANP cleavage product, F-R-Y, is rapidly degraded further by cleavage of the R-Y bond. Cross-linking studies with 125I-ANP in the presence of sulfhydryl-modifying agent indicate that IDE activity is inhibited at the level of initial substrate binding whereas metal-ion chelating agents only prevent hydrolysis. On the basis of its structural and enzymatic properties, IDE exhibits striking similarity to a number of recently-described endopeptidases.

Amino Acid Sequence↗

Interendothelial junctions during blood-brain barrier development in the rat: morphological changes at the level of individual tight junctional contacts.

The endothelium of brain capillaries represents the structural basis for the blood-brain barrier in vertebrates. Individual endothelial cells are linked by a continuous belt of complex tight junctions (zonulae occludentes). Hydrophilic solutes and macromolecules are believed to cross the barrier through specific carrier mechanisms. Unspecific paracellular ionic leak is thought to be very low. In rats the blood-brain barrier is not fully developed until postnatal day 24. We investigated the ultrastructure of the developing blood-brain barrier at 5 developmental stages between embryonic day 17 and young adults. The use of high power goniometric tilting of ultrathin sections allows one to gather information about the exact relationship between two opposing membranes throughout the entire length of the cleft. Our results suggest that the maturation of blood--brain barrier interendothelial clefts is accompanied by the establishment of a characteristic ratio of 'narrow zone' (complex tight junctions) to 'wide zone' (15-20 nm), and of a typical cleft length. Membrane separation larger than 20 nm disappear and individual tight junctional contacts undergo structural changes.

Animals↗

Intermediate filaments in Sertoli cells.

Using immunohistochemical techniques both at light and electron microscopic levels, the arrangement and distribution of intermediate filaments in Sertoli cells of normal testis (in rat and human), during pre- and postnatal development (in rabbit, rat, and mouse) and under experimental and pathological conditions (human, rat), have been studied and related to the pertinent literature. Intermediate filaments are centered around the nucleus, where they apparently terminate in the nuclear envelope providing a perinuclear stable core area. From this area they radiate to the plasma membranes; apically often a close association with microtubules is seen. Basally, direct contacts of the filaments with focal adhesions occur, while the relationship to the different junctions of Sertoli cells is only incompletely elucidated. In the rat (not in human) a group of filaments is closely associated with the ectoplasmic specializations surrounding the head of elongating spermatids. Both in rat and human, changes in cell shape during the spermatogenic cycle are associated with a redistribution of intermediate filaments. As inferred from in vitro studies reported in the literature, these changes are at least partly hormone-dependent (vimentin phosphorylation subsequent to FSH stimulation) and influenced by local factors (basal lamina, germ cells). Intermediate filaments, therefore, are suggested to be involved in the hormone-dependent mechanical integration of exogenous and endogenous cell shaping forces. They permit a cycle-dependent compartmentation of the Sertoli cell into a perinuclear stable zone and a peripheral trafficking zone with fluctuating shape. The latter is important with respect to the germ cell-supporting surface of the cell which seems to limit the spermatogenetic potential of the male gonad.

Animals↗

[Intralesional therapy with natural interferon-beta in refractory squamous epithelial cancers of the ENT area].

It has been the aim of the present investigation to study the effect of intratumorally applied human fibroblast interferon (nIFN-beta; Fiblaferon 5 for the first two weeks, and Fiblaferon 3 three times a week) in a phase-II clinical trial of thirteen patients with advanced head and neck squamous cell carcinomas. All of the patients had failed established therapeutic modalities before and could not be treated by conventional procedures. nIFN-beta was injected intratumorally and its effect on tumour size was assessed by an independent, second observer as well as via CT and MR imaging. All assessments were done prior to treatment, 8 weeks after beginning treatment and at 16 weeks. Three female and ten male patients with primary tumours of the hypopharynx (n = 5), the larynx (n = 4), the oropharynx (n = 1), the glandula submandibularis (n = 1), the oral cavity (n = 1) and the oesophagus (n = 1) have undergone outpatient treatment three times a week. Tumour size showed no change in six patients while progressive disease occurred in seven cases after eight weeks of treatment. Radiological findings did not change in the nine patients continuing treatment while five showed progressive disease. There were no serious local or systemic side effects due to the intratumoral nIFN-beta treatment. The survival time was 9.73 months after the onset of nIFN-beta treatment.

Adult↗