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Biomedical subjects

H Weber

Publications and source records attributed to H Weber.

At least 703 records · Page 39Linked to original sources
PubMedDate not supplied

Permanent bile duct cannulation in the monkey. A model for studying intestinal absorption.

Our aim has been to obtain an experimental model where the test animal is subjected to the least amount of stress and restraint, and can serve for the repeated sampling of biliary excretion over a prolonged period of time. By using a special end-piece at the outer terminals of the two cannulas the monkeys could be given full freedom after experimentation. During the course of the study it was found that insertion of the cannula into the common bile duct led to the development of collateral pathways for passage of bile around the point of insertion. This adaption reaction for the restoration of a normal bile channel would seem to be characteristic of Rhesus monkeys, for we did not encounter it in similar experiments on dogs and minipigs. The experimental model described is intended to serve for the determination of intestinal absorption of compounds that are mainly excreted via the bile. Results with radioactive ergotamine are presented.

Animals↗
PubMedDate not supplied

Detection of mutations in bacteria and of DNA damage and amplified DNA sequences in mammalian cells as a systematic test strategy for elucidating biological activities of chemical carcinogens.

The interdisciplinary evaluation of risks from carcinogens utilizes, inter alia, data on the activities of the compounds in short-term assays. A systematic approach is being used to determine mutagenesis in bacteria (the study of direct activities and specific modes of metabolic activation), DNA damage within primary mammalian cells (DNA single-strand breaks and persistence of damage, by a method extendable to the in vivo situation) and amplified DNA sequences in cultured cells (as an endpoint probably relevant to carcinogenesis). This test combination was expected to reduce some of the shortcomings of other batteries of tests, which suffer from a lack of appropriate metabolic conversion of compounds, irrelevancy of genetic endpoints and pharmacokinetic limitations. Furthermore, as each assay in the test strategy differs from the others only by one of the parameters described above, a reasonable understanding of divergent test results from assay to assay was anticipated. Several substances were investigated to elucidate why their activities in short-term assays and in carcinogenesis experiments do not correlate. The substances were N-nitrodimethylamine, for which formaldehyde is the reactive intermediate in bacterial mutagenesis but not in mammalian cells or in vivo, N-nitrosodiethanolamine, a carcinogen that must be activated by external alcohol dehydrogenase to be mutagenic in bacteria, N-nitrosodialkylamines, with unique organotropism in vivo for which organ-specific activation was studied in vitro, N-nitroso compounds that are inactivated in vivo but not in vitro, and components of the aristolochic acid mixture which may be metabolized oxidatively or reductively, as well as numerous miscellaneous compounds that were expected to be genotoxins on account of their chemical structure. In addition to the assessment of genotoxicity, the results obtained in individual tests of this strategy yield important data on mechanisms of activity, such as organ-specific activation and deactivation, species variations, in vitro/in vivo correlation and persistence or repair of damage.

Animals↗
PubMedDate not supplied

Is sequence conservation in interferons due to selection for functional proteins?

The human alpha-interferon (IFN-alpha) gene family consists of at least 14 potentially functional non-allelic members; the amino acid sequences they encode differ from each other by up to approximately 20% of their residues. Human IFN-beta, which is encoded by a single gene, is distantly related to the IFN-alpha family; it differs in 67% of its residues from IFN-alpha 2. There is considerable evidence that IFN-alpha and -beta compete for the same receptors on their target cells. Comparison of 14 non-allelic human IFN-alpha sequences and the IFN-beta sequence has revealed that 37 of 166 residues are completely conserved and that several of these are arranged in clusters, for example at positions 29-33, 47-50 and 136-150. It is commonly held that evolutionary conservation of amino acids indicates that the residues in question are essential for function. To test this hypothesis in the case of IFNs, we have introduced single site-directed point mutations into the strictly conserved codons 48 and 49 of the IFN-alpha 2 gene which form part of the longest uninterrupted cluster (position 47-50). We report here that the mutant proteins, containing Tyr, Ser and Cys instead of Phe48, or His instead of Gln49, have biological activities indistinguishable from those of wild-type IFN-alpha. In addition, when Glu62, a residue conserved in all known alpha and beta IFNs of man, mouse and cattle, was replaced by Lys, antiviral activity remained unchanged.

Amino Acid Sequence↗
PubMedDate not supplied

[Dimensional changes of polyethylene acetabuli in Müller's hip endoprosthesis. Report on measurement methods and their clinical significance].

The dimensional changes of hip sockets of total endoprosthesis of the Müller Type are subject of this article. Regular-anterior/posterior radiographs of the pelvis were taken to determine the orientation of the center of the prosthetic head in relation to the wire marker of the poly(ethylene) cup. Further measurements were done using casts of worn acetabular cups gained at revisional surgery. The possible errors of measurements of both methods are discussed. Both, creep and wear contribute to the dimensional changes of the hip sockets, the proportional amount of each mechanism is not known. Data from laboratory examinations suggest a relatively high rate of creep in the early time of function. With longer periods the dimensional changes are predominantly caused by wear. In the beginning of joint function our measurements show a high rate of the yearly dimensional change. The shift of the head amounted 0.5 mm per year and diminished after five years to rates of 0.15 to 0.2 mm. All dimensional changes that exceed a shift to the head of 0.2 mm per year are considered to be unfavourable and to contribute to loosening.

Hip Joint↗
PubMedDate not supplied

Long-term study of the distribution of soluble chromate-51 in the rat after a single intratracheal administration.

Soluble chromate-51 (as sodium dichromate dihydrate) was applied intratracheally in rats, after which distribution of radioactivity was followed for 40 d by autoradiograph and gamma scintillation counting. Doses were 0.01 and 0.25 mg/kg in physiological saline solution. After administration of a 0.25-mg/kg dose, lung radioactivity declined rapidly for 2 to 3 d, at which time about a third of the total dose remained in the lung. The radioactivity in the lung was localized mainly intracellularly in the parenchyma. Microautoradiography indicated that the 51Cr was localized mostly in the type II alveolar cells. At the end of the experiment (40 d after administration), approximately 10% of the applied dose was found in the lung. The highest 51Cr quantities and concentrations were determined in the lung throughout. In the blood serum, the decline of radioactivity concentration was characterized by an apparent half-life of 3 to 4 d for the period from 2 to 15 d. The concentration time courses for the other tissues and organs indicated longer apparent half-lives, ranging from 14 to 50 d. Kidney, erythrocytes, and testis maintained their Cr levels for a period of 10 to 15 d, after which the decrease of concentration became evident. The results obtained at the lower dose level of 0.01 mg/kg were largely dose-proportional to those obtained at the higher dose level of 0.25 mg/kg.

Animals↗
PubMedDate not supplied

Modulation of in vitro angiogenesis in a three-dimensional spheroidal coculture model for bone tissue engineering.

One of the major challenges in tissue engineering of bone substitutes remains vascularization of the transplant. We have developed a three-dimensional collagen-based coculture system to assess interactions between human endothelial cells (hECs) and human osteoblasts (hOBs) in vitro. Human umbilical vein endothelial cells (HUVECs) were grown as three-dimensional multicellular spheroids and seeded in a collagen matrix to assess sprouting of the spheroids, that is, formation of tubelike structures resembling early capillaries. Direct cell contact between hOBs and HUVECs was established by incorporating hOBs into the EC spheroids, thus forming heterogeneous cospheroids. Spatial organization of cospheroids and sprout configuration were assessed by immunohistochemical wholemount staining techniques and confocal laser microscopy. Cumulative sprout length of spheroids was quantitatively analyzed by digital imaging planimetry. In this model HUVECs and hOBs formed heterogeneous cospheroids with distinct spatial organization. The ability of HUVEC spheroids to form tubelike structures on angiogenic stimulation with vascular endothelial growth factor and basic fibroblast growth factor was suppressed in heterogeneous HUVEC/hOB cospheroids. The model system introduced in this study may be useful to assess the mechanisms involved in regulating angiogenesis during bone formation and to further investigate the mechanisms by which heterotypic cell-cell interactions inhibit endothelial tube formation for applications in bone tissue engineering.

Bone Substitutes↗
PubMedDate not supplied

The design and use of a dual-frequency surface coil providing proton images for improved localization in 31P spectroscopy of small lesions.

Nuclear magnetic resonance (NMR) spectroscopy of small lesions is restricted by the difficulties of localizing the surface coil with respect to the lesion and the problem of ensuring that signal is only obtained from the lesion and not from surrounding tissue. A double-tuned coil has been developed that permits NMR proton images to be obtained from a region of interest, prior to carrying out 31P spectroscopy of the same region with the same coil, without the need for further adjustment. The coil provides a means of accurately localizing the region from which the 31P signal is obtained, whilst offering a means of accurately applying 31P signal localization methods, and the possibility of making corrections for the nonuniform sensitivity of a given surface coil. The coil makes use of two parallel resonant circuits, with independent rf connections, but sharing a common coil. Simulated shorted and open circuit lambda /4 cables are used, respectively, to open circuit each circuit at the resonant frequency of the other circuit and ensure that the simulated lambda /4 line is short circuited for each circuit at the circuit's resonant frequency. At 63.6 MHz, the Q of the coil was 190 unloaded and 90 loaded, and at 25.7 MHz the Q was 210 unloaded and 140 loaded, for a 4-cm-diam coil. The coil has been used to obtain proton images and 31P spectra. A circuit employing only one input was also developed.

Humans↗
PubMedDate not supplied

p38 map kinase is expressed in the pancreas and is immediately activated following cerulein hyperstimulation.

BACKGROUND: The pathophysiology of pancreatitis and the pancreatic stress response are not well understood. In the pancreas, mitogen-activated protein kinase (MAPK) and stress-activated protein kinase (SAPK) are reportedly regulated by secretagogue stimulation and hyperstimulation. However, no data exist on the expression and regulation of pancreatic p38 Map kinase. AIMS: Pancreatic expression of p38 Map kinase and MAPK, SAPK and p38 regulation during pancreatic stress were investigated. METHODS: For hyperstimulation and secretory stress, cerulein was given intravenously, while hyperthermia preconditioning stress was induced by whole body hyperthermia (42 degreesC). RESULTS: In addition to MAPK and SAPK, p38 Map kinase was found to be expressed in the rat pancreas. Cerulein regulated all kinases time- and dose-dependently. MAPK and p38 Map kinase showed basal activity and were further activated at low cerulein doses. SAPK had no basal activity and its activation required maximal secretory to supramaximal amounts of cerulein. Cerulein hyperstimulation, inducing pancreatitis, activated p38 more rapidly than SAPK and more strongly than MAPK. In contrast to cerulein hyperstimulation stress, hyperthermia stress only activated p38 Map kinase. CONCLUSIONS: p38 Map kinase is expressed in the pancreas and is most rapidly activated following cerulein hyperstimulation. Both SAPK and p38 Map kinase are possibly important regulators during the onset of cerulein pancreatitis.

Animals↗
PubMedDate not supplied

Release of hyaluronan and laminin into pancreatic secretions.

BACKGROUND: Development of fibrosis characterizes chronic pancreatitis. As it results from deposition of extracellular matrix (ECM) proteins such as hyaluronan (HA) or laminin, the release of these ECM components into blood or pancreatic secretion may be enhanced during the course of chronic pancreatitis. PATIENTS, MATERIAL AND METHODS: Using immunoassays for HA and laminin, the concentration for these ECM components was measured in pancreatic juice and serum samples from 20 patients with and 20 patients without chronic pancreatitis. Pancreatic calculi of varying size and weight obtained from 13 patients with chronic pancreatitis were also examined for the content of ECM components. Tissue samples from normal pancreas and those showing chronic pancreatitis were investigated immunocytochemically with an antibody to HA synthetase (HAS). RESULTS: After stimulation with secretin high levels of ECM components were found in the initial washout period in chronic pancreatitis patients as well as in controls. HA levels, however, were seen seven times higher in patients with chronic pancreatitis (mean +/- SEM; 734 +/- 301 vs. 95 +/- 15 microg/l; p < 0.01). Serum HA levels correlated with the duration of chronic pancreatitis and with the levels of HA in pancreatic juice. HA and laminin were detected in the supernatants of pancreatic calculi (laminin 0.70 +/- 0.30 U/l; HA 275 +/- 85 microg/l). Immunocytochemically, strong staining for HAS was found in the duct epithelium and in centroacinar cells of chronic pancreatitis specimens. CONCLUSION: Demonstration of increased amounts of HA in pancreatic juice of chronic pancreatitis patients stimulated with secretin suggests enhanced production of this ECM component in the chronically inflamed pancreas. The source of HA appears to be the pancreatic ductal epithelium.

Calculi↗
PubMedDate not supplied

Changes in glomerular and cortical tubular cAMP metabolism in kidneys from rats with unilateral ureteral obstruction.

Obstructive uropathy is associated with changes in several renal functions. As some of these are mediated by cAMP, we examined whether changes in cAMP metabolism could contribute to the pathophysiology of unilateral ureteral ligation in rats. We found that basal adenylate cyclase in the cortex of the obstructed kidney doubled after 3-7 days, but the response to NaF and parathyroid hormone was decreased. Similarly, in vivo infusion of parathyroid hormone resulted in lower cAMP levels in the cortex of the obstructed kidney. Parathyroidectomy or pretreatment with beta-adrenergic blocker had no effect. Prostaglandin inhibition by indomethacin decreased, but did not abolish, the differences. On the other hand, basal adenylate cyclase in glomeruli from contralateral kidneys was higher. Pretreatment with indomethacin reduced the basal activity in contralateral glomeruli, and led to increased degrees of stimulation with parathyroid hormone and prostaglandins. Furthermore, we demonstrated that isolated glomeruli contain cAMP-dependent protein kinase that is found predominantly in the 30,000 g supernatant fraction and that by DEAE-cellulose chromatography has the characteristics of a type II kinase. In glomeruli from rats with unilateral ureteral ligation, the distribution and degree of activation of the cAMP-dependent protein kinase are affected differently on the ligated and contralateral sides, probably reflecting the change in glomerular cAMP generation. These results indicate that changes in cAMP metabolism may contribute to the altered cortical tubular function in unilateral ureteral ligation and may be partially related to enhanced prostaglandin synthesis in the obstructed kidney. On the other hand, the higher adenylate cyclase activity and the change in cAMP-dependent protein kinase activity in glomeruli from the contralateral kidney may in part reflect increased PGE2 production by these glomeruli. The results support the concept that similar to their in vitro action, locally generated prostaglandins may in vivo affect cortical tubular function by influencing the tubular cAMP system while those generated in the glomerulus alter glomerular cAMP metabolism.

Adenylyl Cyclases↗
PubMedDate not supplied

Sugars as signal molecules in plant seed development.

Higher plants as sessile organisms react very flexible to environmental changes and stresses and use metabolites like glucose, sucrose and nitrate not only as nutrients but also as signals as part of their life strategies. The role of metabolites as signal molecules has attracted considerable interest during recent years. Data reviewed here for developing plant seeds suggest a trigger function of especially sugars also in development in that metabolic regulatory control can override developmental regulation, i.e., the developmental programme only continues normally if a certain metabolic state is sensed at a given time point in a given cell or tissue. Several experimental strategies have provided mainly correlative evidence that certain sugar levels and/or the resulting changes in osmotic values are necessary within defined tissues or cells to maintain a distinct stage of differentiation or to proceed with the developmental programme. In young legume seeds, but certainly also in other tissues, a high hexose (probably mainly glucose) level seems to maintain the capacity of cells to divide whereas - later in seed development - a certain sucrose level is necessary to induce storage-associated cell differentiation. A major determinant of embryo hexose levels in young legume seeds is an apoplastic invertase preferentially expressed in the inner cell layers of the seed coat. The enzyme cleaves the incoming photoassimilate sucrose into glucose and fructose. During development the tissue harbouring the invertase is degraded in a very specific spatial and temporal pattern as part of the developmental programme and is thus creating steep glucose gradients within the cotyledons. These gradients can be measured at nearly cellular resolution and were found to be correlated positively with cell division rate and negatively with cell differentiation and storage activities. A hexose and a sucrose transporter accumulating only in the epidermal cell layer of the cotyledons seem to be essential in creating and maintaining these gradients. To gain further insights into the role of metabolites, especially sugars, as triggers of developmental processes we foremost have to identify receptor molecules already characterised in yeast, and to describe and understand the signal transduction networks involved.

Glucose↗
PubMedDate not supplied

A comparison of laser-welded titanium and conventional cast frameworks supported by implants in the partially edentulous jaw: a 3-year prospective multicenter study.

PURPOSE: The purpose of this prospective multicenter study was to evaluate and compare the clinical performance of laser-welded titanium fixed partial implant-supported prostheses with conventional cast frameworks. MATERIALS AND METHODS: Forty-two partially edentulous patients were provided with Brånemark system implants and arranged into 2 groups. Group A was provided with a conventional cast framework with porcelain veneers in one side of the jaw and a laser-welded titanium framework with low-fusing porcelain on the other side. The patients in group B had an old implant prosthesis replaced by a titanium framework prosthesis. The patients were followed for 3 years after prosthesis placement. Clinical and radiographic data were collected and analyzed. RESULTS: Only one implant was lost, and all prostheses were still in function after 3 years. The 2 framework designs showed similar clinical performance with few clinical complications. Only one abutment screw (1%) and 9 porcelain tooth units (5%) fractured. Four prostheses experienced loose gold screws (6%). In group A, marginal bone loss was similar for both designs of prostheses, with a mean of 1.0 mm and 0.3 mm in the maxilla and mandible, respectively. No bone loss was observed on average in group B. No significant relationship (P > 0.05) was observed between marginal bone loss and placement of prosthesis margin or prosthesis design. CONCLUSION: The use of laser-welded titanium frameworks seems to present similar clinical performance to conventional cast frameworks in partial implant situations after 3 years.

Adolescent↗
PubMedDate not supplied

Immediate postextraction implant placement with root-analog stepped implants: surgical procedure and statistical outcome after 6 years.

The present study investigated 124 stepped-screw implants (gritblasted and acid-etched surface) placed in 104 patients immediately after tooth extraction or implant explantation and followed between August 1990 and December 1996. Implants of varying diameters and lengths were used to cover a wide range of indications in both the maxilla and mandible; 68% of the implants supported single-tooth replacements. The study parameters included Plaque Index, Gingival Index, probing depth, Periotest values, and peri-implant bone loss. Statistical analysis according to Kaplan-Meier revealed a 97% survival rate.

Acid Etching, Dental↗
PubMedDate not supplied

Surgical treatment of iliofemoral vein thrombosis technical aspects. Possible secondary interventions.

From October 1982 to February 1989 148 patients underwent venous thrombectomy. Priority for surgery was given especially in patients under 40 years with posttraumatic, postoperative and postpartum thrombosis where lysis was not possible. Our standardized operative technique includes atraumatic exposure of the vessels, clot extraction by balloon catheter and ring stripper, endoscopic control of the lumen and establishment of a temporary arteriovenous fistula. Postoperative angiography revealed that more than 10% of the patients needed secondary dilatation of iliac vein stenosis which can be carried out easily at the time of closing the fistula. Functional and anatomical parameters as well as the clinical outcome after 12 months show good to excellent results which confirm venous thrombectomy as a useful treatment modality at an acceptable risk level.

Adult↗
PubMedDate not supplied

The marginal fit of cemented galvanoceramic crowns.

Galvanoceramic restorations were constructed for five extracted teeth. Following cementation, the margins were photographed (magnification X 33) and the prints mounted to produce a continuous image of the entire margin. Cement film thickness measurements were made at 0.1-mm intervals. The five cemented restorations were then embedded in resin, sectioned longitudinally, and examined under a microscope (X 125). The mean gap at the restoration margin, as measured by each technique, was 18 microns and 19 microns, respectively. These results were consistent with the clinical impressions of cemented galvanoceramic restorations completed at the University of Tübingen.

Crowns↗
PubMedDate not supplied

The durability of bioprostheses in young people. Long-term results with intra- or extracardiac implanted porcine valves.

Forty two children and two young adults who were long term survivors of either intracardiac or extracardiac valve replacement with glutaraldehyde porcine valves form the basis of this report. The follow-up period varied from 6 months to 9 years. Ten of eleven intracardiac valves developed some dysfunction--the eleventh patient died from other causes. Of a total of 36 extracardiac valved conduits in the Rt side of the heart, four have needed replacement and an additional four will require replacement in due course. The probability of an event free performance of an intracardiac porcine valve is zero at 5 years. Four extracardiac valves there is in an 80% expectancy at 5 years and a 12% at 8 years of trouble free existence.

Adolescent↗