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Biomedical subjects

A Schmidt

Publications and source records attributed to A Schmidt.

At least 379 records · Page 21Linked to original sources

Expression of alpha v and beta 3 integrin subunits in rat osteoclasts in situ.

Recent findings suggest that the vitronectin receptor, a member of the integrin family, plays an important role in the attachment of osteoclasts to bone matrix. We report here the localization by in situ hybridization of the mRNA for the alpha and beta subunits of the vitronectin receptor in rat bone sections. To generate the rat-specific RNA probes used in this study, we cloned cDNA fragments of integrin chains alpha v, beta 3, and beta 5 by the polymerase chain reaction from rat cDNA. These fragments share 86-91% homology with the respective human sequences. In situ hybridization localized the alpha v and beta 3 mRNAs to regions undergoing extensive bone resorption. The histologic appearance and prestaining of bone sections for tartrate-resistant acid phosphatase (TRAP) indicated the presence of these mRNAs in osteoclasts. These observations support immunohistochemical findings that osteoclasts express high levels of the vitronectin receptor, confirm the identity of this receptor as integrin alpha v/beta 3, and suggest that osteoclasts may actively synthesize these molecules.

Amino Acid Sequence↗

Tumor necrosis factor-alpha, interleukin 1, eicosanoid, and hydrogen peroxide release from macrophages exposed to glove starch particles.

The inflammatory mechanisms leading to glove starch powder peritonitis are still unclear. This study was designed to examine the secretory potential of macrophages exposed to starch powder particles. Rat peritoneal macrophages and human monocytes were incubated in vitro with starch particles obtained from three commonly used surgical gloves. It was found that macrophages and monocytes released large amounts of tumor necrosis factor-alpha, interleukin 1, prostaglandin E2, thromboxane B2, and hydrogen peroxide. Release of these inflammatory mediators was associated with progressive cell death of macrophages. These data indicate that postoperative peritonitis and subsequent granuloma formation initiated by glove powder particles may be mediated and maintained, at least in part, by macrophage-derived cytokines, eicosanoids, and reactive oxygen intermediates.

Animals↗

Acute infection of Macaca nemestrina by human immunodeficiency virus type 1.

The pigtail macaque (Macaca nemestrina) has a marked sensitivity to infection by simian immunodeficiency virus and human immunodeficiency virus type 2 (HIV-2). On this basis, we previously studied this species' susceptibility to HIV-1 and demonstrated infection in six macaques inoculated with either cell-associated HIV-1 or cell-free virus alone. This report expands upon our initial in vitro and in vivo findings. Five laboratory-adapted and one primary clinical strain of HIV-1 replicated in vitro in human and M. nemestrina peripheral blood mononuclear cells (PBMCs). Replication was enhanced when CD4+ purified PBMCs were infected and inhibited when PBMC cultures were treated with zidovudine. All six macaques demonstrated HIV-1 infection of PBMCs from 2 to 8 weeks after inoculation but nearly all PBMC cultures were negative from weeks 10 to 40. Polymerase chain reaction showed HIV-1 gag DNA in the PBMCs of all infected macaques, including times when the macaques were culture negative. All macaques developed and maintained antibodies to gag and envelope HIV-1 proteins from week 4 after inoculation through the period of observation. Five macaques showed neutralizing antibody. These findings suggest that M. nemestrina can be infected by cell-free and cell-associated HIV-1. This model of acute HIV-1 infection may help in evaluating the pathogenesis of HIV-1 replication and candidate vaccines and therapies.

Acute Disease↗

ESWL and the future of stone management.

Based on optimal efficacy regarding disintegration and stone clearance, combined with minimal invasiveness, extracorporeal shockwave lithotripsy (ESWL) represents the first choice therapy for urolithiasis. Further developments in ESWL have related more to economic aspects than to improvement of disintegration efficacy or reduction of side effects. Routine indications for ESWL are well known and widely accepted. Its limitations are also well established: silent calyceal stones, calyceal diverticula stones, nephrolithiasis in horse-shoe kidneys, medullary sponge kidney, and residual fragments after ESWL. Although endourology provides new, less invasive and traumatic means of stone retrieval or disintegration, including laser lithotripsy, small ureteroscopes and actively deflectable uretero- and pyeloscopes, indications for an aggressive approach in such cases are limited to those who are symptomatic. In the case of distal ureteral calculi ureteroscopy in traureteral laser-induced shockwave lithotripsy open up new and interesting possibilities for the future.

Animals↗

Examination of the stability in the talocrural joint with special consideration of the function of the peroneal tendon sheath.

The structure and variations of the peroneal tendon sheaths of 69 formaldehyde-fixed cadaver ankle joints were studied both macroscopically and microscopically. The peroneal tendon sheath is a structure which is adapted to the mechanical requirements of the region overlying the lateral malleolus. It serves simultaneously as a guide and restraint for the peroneal tendons and as a lateral stabiliser of the upper ankle joint. This conclusion is based on examinations of thickness as well as light and polarisation microscopy. Mechanical cadaver studies of the stability of 24 ankle joints underlined the importance of the peroneal tendon sheath in stabilising the upper ankle joint. Defined lesions followed by suturing of the ligamentous structures and peroneal tendon sheath were performed with a simultaneous rotation drawer effect. A lateral opening was documented radiologically. It has been demonstrated that, although the thickness of the peroneal tendon sheath differs greatly from individual to individual, suturing is always important to stabilise the ankle joint after plantar flexion-supination-adduction trauma.

Adult↗

Interaction of the competitive AMPA receptor antagonist NBQX with hexobarbital.

IP administration of hexobarbital to rats caused a mean sleeping time of 93.6 min (SD 21.5). IV infusion of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX) at a dose rate of 0.11 mg/kg/min starting 30 min after administration of hexobarbital prolonged the mean sleeping time to 132.2 min (SD 14.9). Dose rates of 0.33 and 1.10 mg/kg/min prolonged the mean sleeping times to 176.4 min (SD 33.3) and 444.1 min (SD 72.0), respectively. Measured 180 and 450 min after the start of the study, there were no differences in the plasma concentrations of hexobarbital in groups receiving hexobarbital alone compared to groups receiving the high-dose rate of NBQX starting 30 min after administration of hexobarbital. The present results demonstrate that by IV infusion NBQX dose dependently prolonged the sleeping time of hexobarbital. There were no indications of interactions on hexobarbital elimination of either isomer. It is therefore likely that NBQX acts synergistically with hexobarbital to depress the central nervous activity.

Animals↗

[Growth factor-induced stimulation of proteoglycan synthesis in corneal endothelium cells].

BACKGROUND: Cultured bovine corneal endothelial cells (CEC) synthesize heparan sulfate and dermatan sulfate containing proteoglycans and distribute them between different compartments. METHODS AND RESULTS: [35S]sulfate labelled proteoglycans are found associated with the cell layer, secreted into the culture medium and deposited into the underlaying extracellular matrix. In the presence of basic fibroblast growth factor (bFGF)-a strong mitogen for CEC-subconfluent cells incorporate [35S]sulfate into the sulfated proteoglycans at a rate three times higher as compared with the proteoglycans of CEC in the absence of bFGF. The enhanced proteoglycan synthesis is accompanied with a shift in the proteoglycan distribution pattern. While in control cells the cell-associated heparan sulfate accounts for about 30% of the total glycosaminoglycans under the influence of bFGF the HS percentage increases to approximately 60%. CONCLUSIONS: CEC synthesize and deposit endogenous bFGF into the extracellular matrix. Heparitinase treatment of the extracellular matrix releases bFGF activity which is able to stimulate the 35S incorporation into proteoglycans in a comparable manner as exogenous bFGF but does not influence the proteoglycan distribution pattern. Pretreatment of the matrix-bound bFGF activity with polyclonal antibodies against bFGF abolishes its stimulating activity.

Animals↗

Loss of cathepsin B activity in alveolar macrophages after in vitro quartz phagocytosis.

Bovine alveolar macrophages were incubated up to 20 h with DQ12 quartz particles, either in untreated native form or pretreated with dipalmitoyl lecithin. The content of cathepsin B and N-acetylglucosaminidase was measured in the culture supernatant and in the cells. After incubation, a loss of about 50% of the total cathepsin B activity in the culture dish was observed, whereas no influence on total N-acetylglucosaminidase content occurred. Loss of cathepsin B activity was completely prevented by the pretreatment of quartz with the surfactant component dipalmitoyl lecithin. Similarly, a complete abrogation of the quartz effect on cathepsin B was noted when the cells were incubated with quartz in the presence of NH4Cl in order to prevent phagosome-lysosome fusion. There was also no influence on cathepsin B activity when a lysosome-rich fraction, prepared from alveolar macrophages, was incubated together with quartz. It was concluded that the reduction of cathepsin B activity was related with the intralysosomal deposition of quartz particles.

1,2-Dipalmitoylphosphatidylcholine↗

Lasertripsy of ureteral calculi using pulsed-dye laser with automatic shut-off after tissue contact.

Since June 1991, 54 patients with ureteral calculi (13 upper, 18 middle, and 23 distal) have been treated in our department using a flashlamp-pumped tunable-dye (rhodamine 6G) laser with a wavelength of 594 nm with an energy at the distal fiber tip between 30 and 120 mJ. The fiber core diameters were 200 and 300 microns. By spectral analysis of the reflected light, immediate shut-off of the laser was obtained after tissue contact. In average, 1599 impulses at a mean energy of 76.4 mJ were applied. In 32 cases (59%), complete disintegration was achieved. In 22 cases (41%), partial disintegration was noted, leading to retrograde mobilization of the fragments followed by SWL in 16 patients. Ureteroscopic extraction of fragments was performed in six patients. All patients were rendered stone free after 6 weeks. Because of the ureteroscopic manipulation, mucosal lesions were found in five patients, but no trauma attributable to the action of the laser was seen. In 42 patients, a double-J stent was placed after the procedure. Lasertripsy using a pulsed-dye laser with automatic shut-off after tissue contact is a safe and effective approach that offers a new aspect in the noninvasive treatment of recalcitrant ureteral calculi in our department.

Automation↗

Early radical treatment of pancraniofacial synostosis.

Premature fusion of all major cranial and facial sutures, termed pancraniofacial synostosis by us, was first described as "Kleeblattschädel deformity," but can also be found in anomalies such as Crouzon's disease, Apert's syndrome, Pfeiffer's syndrome, and severe forms of plagiocephaly. This rare craniofacial anomaly often presents an immediate threat to life right after birth. Early subtotal craniectomy frequently combined with frontoorbitofacial advancement must be performed to decrease intracranial pressure, preserve vision, and open up the blocked upper airway. Concomitant hydrocephaly is shunted preoperatively for internal decompression. Eleven patients with pancraniofacial synostosis underwent craniofacial surgery in infancy or early childhood. Only shunting of the hydrocephalus was done in 1 child. Two children died in the course of an emergency procedure and 2 children died after secondary operations for miniplate removal and revision of a valve shunting the hydrocephalus several months after the initial successful craniofacial surgery. The remaining 8 children have developed satisfactorily so far. Further corrective surgeries had to be performed in 2 patients. Good functional and aesthetic improvement could be obtained. In view of the high mortality especially after emergency procedures, we believe that early total craniofacial mobilization should be reserved for severe cases where the natural course is dismal without immediate intervention and temporary procedures such as shunting and tracheostomy are not sufficient. Elective surgeries after the age of 3 months can be performed safely in milder cases.

Cerebrospinal Fluid Shunts↗

Simultaneous construction of an internal and external nose in an infant with arhinia.

We report on the simultaneous construction of an internal and external nose in an infant born with arhinia. The indication for this very early reconstruction was due to respiratory distress and the associated feeding problems. It was possible to create two nasal cavities separated by a septum and to form an external nose from pre-expanded skin and a secondary arm flap for the tip supported by a frontal bone flap with intrinsic growth potential and auricular cartilage grafts for the tip. The 4-year-old child has excellent function of the nose with an acceptable appearance. Her psychological development is normal. Respiratory distress and associated feeding problems necessitated the use of oropharyngeal and orogastric tubes in a female infant born without a nose (arhinia). Over a period of many weeks, with attempts to remove the tube resulting in aspiration, we decided to create a functional nasal airway and an external nose simultaneously at this early stage. At the age of 20 weeks, two nasal cavities were created by using a buccal sulcus incision and connected to the existing nasopharynx and partially lined with split skin grafts. An external nose was created using the expanded midfacial skin and supporting it, an osteoperiosteal flap from the frontal bone. Later, a Tagliacozzi flap had to be added for the nasal tip. The newly constructed nose functions well and appears to aid favorably in the normal psychosocial development of the now 4-year-old girl.

Female↗

Chemotaxis of polymorphonuclear neutrophils (PMN) in patients suffering from recurrent infection.

PMN function was tested in patients suffering from recurrent infections. In 65 out of 240 patients lack of oxygen radical production or reduced chemotactic activity was found. In most cases the reduction was transient and associated with clinical impairments of the patients. Only a few patients had primary cellular defects. In one of those patients the expression of beta 2 integrins was reduced, while PMN of the other patients expressed beta 2 integrins normally. Thus, cellular defects other than the reduced expression of beta 2 integrins might also result in impaired chemotactic activity.

Adult↗

Analysis of transient-evoked otoacoustic emissions in normal-hearing and hearing-impaired ears.

Transient-evoked otoacoustic emissions (TEOAEs) were measured in 113 normal-hearing and hearing-impaired ears to examine repeatability within a test session, which TEOAE parameter (level, TEOAE level-to-noise or reproducibility) best identified hearing loss and if the TEOAE separated into frequency-specific bands identified hearing loss in a corresponding frequency region. TEOAEs and stimulus levels were found to be very repeatable. For broadband TEOAEs, TEOAE level, TEOAE-to-noise, and % reproducibility were found to identify hearing loss equally well, based on measurement of the area underlying relative operator characteristic curves. Analysis for frequency-specific bands showed that separation of normal-hearing and hearing-impaired ears depended on frequency, with best identification at 2000 and 4000 Hz, identification at 1000 Hz slightly worse, and virtually no separation between normal-hearing and hearing-impaired ears at 500 Hz. Again, all three parameters were essentially equal in identifying hearing loss. Subjective evaluations of presence or absence of TEOAEs was highly correlated between two judges, with good agreement for TEOAEs at 1000, 2000, and 4000 Hz. The findings from this study suggest that TEOAEs will be valuable for clinical use because of their repeatability and identification of hearing-impaired ears.

Acoustic Stimulation↗

The immunosuppressant FK506 inhibits amino acid import in Saccharomyces cerevisiae.

The immunosuppressants cyclosporin A, FK506, and rapamycin inhibit growth of unicellular eukaryotic microorganisms and also block activation of T lymphocytes from multicellular eukaryotes. In vitro, these compounds bind and inhibit two different types of peptidyl-prolyl cis-trans isomerases. Cyclosporin A binds cyclophilins, whereas FK506 and rapamycin bind FK506-binding proteins (FKBPs). Cyclophilins and FKBPs are ubiquitous, abundant, and targeted to multiple cellular compartments, and they may fold proteins in vivo. Previously, a 12-kDa cytoplasmic FKBP was shown to be only one of at least two FK506-sensitive targets in the yeast Saccharomyces cerevisiae. We find that a second FK506-sensitive target is required for amino acid import. Amino acid-auxotrophic yeast strains (trp1 his4 leu2) are FK506 sensitive, whereas prototrophic strains (TRP1 his4 leu2, trp1 HIS4 leu2, and trp1 his4 LEU2) are FK506 resistant. Amino acids added exogenously to the growth medium mitigate FK506 toxicity. FK506 induces GCN4 expression, which is normally induced by amino acid starvation. FK506 inhibits transport of tryptophan, histidine, and leucine into yeast cells. Lastly, several genes encoding proteins involved in amino acid import or biosynthesis confer FK506 resistance. These findings demonstrate that FK506 inhibits amino acid import in yeast cells, most likely by inhibiting amino acid transporters. Amino acid transporters are integral membrane proteins which import extracellular amino acids and constitute a protein family sharing 30 to 35% identity, including eight invariant prolines. Thus, the second FK506-sensitive target in yeast cells may be a proline isomerase that plays a role in folding amino acid transporters during transit through the secretory pathway.

Amino Acid Sequence↗

Paedomorphosis and simplification in the nervous system of salamanders.

Comparative neuroanatomists since Herrick [1914] have been aware of the paradox that the brain of amphibians, especially salamanders, is less complex than one would expect based on their phylogenetic position among the Tetrapoda. Many features of the brain are less differentiated in salamanders than in tetrapod outgroups, including chondrichthyans and bony fishes, and for some brain characters, the salamander brain is even more simple than that of the agnathans. Here, we perform a cladistic analysis on 23 characters of four sensory systems (visual, auditory, lateral line and olfactory) and the brain. Our taxa include myxinoids, lampreys, chondrichthyans, actinopterygians, Latimeria, Neoceratodus and the lepidosirenid lungfishes, amniotes, frogs, caecilians, salamanders and bolitoglossine salamanders. Of the 23 characters we examined, 19 are most parsimoniously interpreted as secondarily simplified in salamanders from a more complex ancestral state, two characters are equally parsimonious under both hypotheses, one character (well developed ipsilateral retinotectal projections) is more complex in bolitoglossine salamanders than in vertebrates generally, and only one character (migration of neurons in the medial pallium) is most parsimoniously interpreted as retention of the plesiomorphically simple condition. Secondary simplification of the salamander brain appears to result from paedomorphosis, or retention of juvenile or embryonic morphology into adulthood. Paedomorphosis is correlated with an increase in genome size, which in turn is positively correlated with cell size, but negatively correlated with cell proliferation and differentiation rates. Available data suggest that, although increasing genome size and paedomorphosis tend to compromise the function of the salamander brain, compensating mechanisms have evolved that may restore or even enhance brain function.

Animals↗

Intra- and perivesical tumor growth in preoperative staging of bladder cancer: the role of transrectal ultrasonography and high resolution magnetic resonance imaging.

Bladder tumors were staged preoperatively before and/or after M-VEC poly-chemotherapy using transrectal ultrasonography and magnetic resonance imaging in 46 patients. The resultant findings were each compared with histomorphologic results. The sensitivity of both methods compared with pathohistology was 88%. Using this technique, the degree of tumor invasion of the bladder wall could be evaluated and the appropriate therapy selected. Further applications included the monitoring of transurethral resection determine its adequacy as a treatment modality.

Adenocarcinoma↗

Constitutive and induced expression of APO-1, a new member of the nerve growth factor/tumor necrosis factor receptor superfamily, in normal and neoplastic cells.

BACKGROUND: APO-1 is a 48 kilodalton transmembrane, cysteine-rich glycoprotein identical with the Fas antigen which belongs to the nerve growth factor/tumor necrosis factor receptor superfamily. Cross-linking of APO-1 induces apoptotic cell death in sensitive cells. EXPERIMENTAL DESIGN: As suggested by our preliminary results, APO-1 expression is not restricted to cells of the hematopoietic lineage. We therefore investigated APO-1 expression in normal human tissues and in various epithelial and nonepithelial tumors. RESULTS: We show by immunohistochemistry that APO-1 is a non-lineage antigen constitutively expressed in a variety of epithelial cells. This includes the basal layers of various squamous epithelia, transitional epithelium and columnar epithelium of the biliary tract and intestine. Among the epithelial cell types of the reproductive system of both genders, APO-1 expression is complex. Except the satellite cells of autonomic ganglia, all cells of the nervous tissue are APO-1-negative. Among mesenchymal cells, constitutive APO-1 expression is rare but detectable in various kinds of activated cells, e.g. fibroblasts, osteoblasts, and subpopulations of endothelial cells. Within the immune system, APO-1 is broadly distributed among histiocytic cells but restricted to minor subpopulations of peripheral T and B cells. Immature T cells, i.e., thymocytes, do not express detectable APO-1-antigen. Expression of APO-1 was induced in phytohemagglutinin activated T cells and in a mammary carcinoma cell line by interferon-gamma alone and in combination with tumor necrosis factor alpha. Consistently, there was an in situ induction of APO-1 in several types of glandular epithelium in microtopographic association with lymphohistiocytic infiltrates. This inflammation-associated APO-1 induction went along with increased expression of this molecule within the lymphocytic compartment of the lesion. In tumors. APO-1 expression was heterogeneous. In comparison to their normal counterparts, some tumors showed abnormal hypo-expression or loss of APO-1. However, abnormal neo-expression was also found. CONCLUSIONS: Tissue distribution, in vitro expression, and reaction upon cytokine-induced activation suggest that APO-1 might not only transmit apoptotic signals but might play a more general role in growth control.

Adult↗