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Biomedical subjects

D Herbst

Publications and source records attributed to D Herbst.

15 recordsLinked to original sources
PubMed2003

Evaluation of a new method to achieve optimal passivity of implant-supported superstructures.

UNLABELLED: Statement of problem. Passive fit of implant-supported superstructures has been suggested as a prerequisite for maintenance of osseo-integration and for successful prosthetic reconstruction. PURPOSE: This study evaluated the degree of fit of superstructures cemented onto titanium abutments, compared to structures cast onto gold cylinders. MATERIAL AND METHODS: An impression was taken and a master cast made of five implants mounted in a stainless steel model. Six similar porcelain fused to metal superstructures with standardised dimensions were then fabricated. One group featured castings onto gold UCLA abutments, while in the other group the structures were cemented onto tapering titanium abutments. Vertical discrepancies between implants and both types of superstructures were measured on at six locations around each implant using a reflex microscope. Measurements were taken after securing the structures to the model with a single screw (torqued to 32 Ncm) placed in various locations and also after tightening all the retaining screws simultaneously to 10 Ncm. RESULTS: With the new single-screw procedure, no significant difference in mean gap size was noted between the two groups. The discrepancies were significantly larger for certain screw locations (1 and 5), indicating that the one-screw test might be an inaccurate way of assessing fit. After tightening all the retaining screws simultaneously to 10 Ncm, the mean gaps were 11.9 microns for the cemented group and 17.8 microns for the cast group. CONCLUSION: Although not statistically significant, cementing of superstructures onto titanium abutments improved the fit up to 50% compared to casting the structures onto gold UCLA-abutments. Tightening one terminal abutment screw and evaluating the discrepancies at the other abutments (one-screw test) distorted the results when evaluating the fit of long-span, implant-supported ceramo-metal superstructures. CLINICAL IMPLICATIONS: The results of this study indicate that cementing superstructures onto titanium abutments will lead to an improved degree of fit, compared to casting superstructures onto gold cylinders. In addition, the one-screw test may not be an accurate method of determining the level of passivity of long-span, ceramo-metal, implant-supported superstructures.

Analysis of Variance↗
PubMed2000

Design and SAR of novel potassium channel openers targeted for urge urinary incontinence. 2. Selective and potent benzylamino cyclobutenediones.

A novel series of benzylamine, potassium channel openers (KCOs) is presented as part of our program toward designing new, bladder-selective compounds for the treatment of urge urinary incontinence (UUI). We have found that the in vitro potency of (R)-4-[3,4-dioxo-2-(1,2, 2-trimethyl-propylamino)-cyclobut-1-enylamino]-3-ethyl-benzo nitrile 1 in the relaxation of precontracted rat detrusor strips can also be obtained with cyanobenzylamine derivative 4 (IC(50) = 0.29 microM) (Figure 3). Addition of a 2-Cl substituted benzylamine moiety and changing the alkylamino substituent of 4 to a t-Bu amine gives 31 (IC(50) = 0.14 microM)-a compound with similar in vitro potency as 4 as well as relaxant activity on bladder smooth muscle in vivo when administered orally (31, ED(50) = 3 mg/kg) in a rodent model of bladder instability. Further modifications, particularly the replacement of the t-Bu amino substituent with a tert-amylamine, gave a similarly active compound 60 (IC(50) = 0.10 microM) which shows excellent in vivo efficacy (ED(50) = 0.6 mg/kg). Moreover, 60, 3-(2,4-dichloro-6-methyl-benzylamino)-4-(1, 1-dimethyl-propylamino)-cyclobut-3-ene-1,2-dione (WAY-151616), shows excellent tissue selectivity for bladder K channels over arterial tissue (60, MAP ED(20) = 100 mg/kg; selectivity: MAP ED(20)/bladder ED(50) = 166). Other manipulations of the benzylamino cyclobutenediones, acylation of the benzylamine, conversion of the benzylamine substituent to a benzamide, homologation of the benzylamine to a phenethylamine, and incorporation of a methyl group at the benzyl carbon, all led to substantial loss of in vitro activity, although some in vivo activity was maintained in the acylated analogues. Compound 60 represents an attractive candidate for development in the treatment of UUI.

Adenosine Triphosphate↗
PubMed2000

Evaluation of impression accuracy for osseointegrated implant supported superstructures.

STATEMENT OF PROBLEM: An often-debated issue still exists concerning implant impression techniques, whether to splint impression copings. Different configurations are available for these copings for a variety of manufacturers' implant systems. PURPOSE: This study evaluated and compared 4 impression techniques in terms of their dimensional accuracy to reproduce implant positions on working casts. MATERIAL AND METHODS: A master model was designed to simulate a clinical situation. Impressions were made using 4 techniques: (1) tapered impression copings not splinted; (2) squared impression copings not splinted; (3) squared impression copings splinted with autopolymerizing acrylic resin; and (4) squared impression copings with a lateral extension on one side not splinted. Reference points machined onto the master model and onto special healing abutments were compared after abutments were transferred to casts using the 4 techniques. Measurements were made using a Reflex microscope, capable of recording in the x-, y-, and z-dimensions. RESULTS: The dimensional accuracy was high and, although statistically significant (P =.022; power > 80%), a maximum distortion difference of only 0.31% was registered. CONCLUSION: The dimensional accuracy of all the techniques was exceptional and the observed differences can be regarded as clinically negligible.

Analysis of Variance↗
PubMed1994

Production of mouse monoclonal antibodies using a continuous cell culture fermenter and protein G affinity chromatography.

The production of anti-alpha-fetoprotein monoclonal antibodies for diagnostic use was carried out in a stirred tank fermenter equipped with a double membrane stirrer for bubble free aeration and continuous medium perfusion. A serum-free medium supplemented with 4 mM L-glutamine and 2.0 milligrams glucose with a protein content of only 780 micrograms/ml was used for the production process. The harvested antibodies were concentrated 50-fold using a tangential ultrafiltration system and were then purified in a one step purification process by protein G affinity chromatography. The purity of the final product (90%) was controlled by SDS-polyacrylamide gel electrophoresis, gel exclusion chromatography and isoelectric focussing. For further quality controls of the product the immunoglobulin subclass and the isoelectric point were determined and the specificity of the purified mAb was tested by RIA using 125I labelled alpha-fetoprotein. 1.87 g of purified monoclonal antibodies were produced (90% purity) within 2 weeks. It was found that the use of this type of stirred tank fermenter combined with a one step purification process using protein G affinity chromatography represents a suitable method for the fast production of medium scale quantities (500 mg-5 g) of monoclonal antibodies for diagnostic use.

Animals↗
PubMed1989

Large-scale preparation of recombinant platelet-derived growth factor AA secreted from recombinant baby hamster kidney cells.

The short isoform of platelet-derived growth factor A (PDGF-A) was expressed in a mammalian host (BHK-21 cell). A cell line was obtained that secreted up to 0.3 micrograms/10(6) cells recombinant PDGF-A chain homodimer/day into the medium. For large-scale production of supernatant, cells were grown either in roller bottles or in 2.5-1 stirred tank fermenters. A simple two-step procedure was developed to purify recombinant PDGF-AA (rPDGF-AA). The first step was adsorption onto porous glass and the final step was reversed-phase high-performance liquid chromatography. The yield was 0.2 mg/l supernatant. A total amount of 20-30 mg pure rPDGF-AA may be obtained from a single fermenter run. Sequence analysis showed the correct amino terminus and no internal proteolytic cleavages. The specific activity was 5 ng/ml for mouse AKR-2B cells. [125I]rPDGF-AA had an affinity constant of approximately 0.5 nM to these cells and 25,000 binding sites were estimated/cell.

Animals↗
PubMed1987

Platelet-derived growth factor. Phorbol ester induces the expression of the B-chain but not of the A-chain in HEL cells.

It was shown previously [(1984) EMBO J. 3, 453-459] that after treatment of the human erythroleukemia cell line HEL with phorbol ester and dimethyl sulfoxide there was a marked increase in the amounts of megakaryocytic markers, especially of platelet alpha-granule proteins and platelet glycoproteins. In order to investigate this differentiation process further we have studied the expression of the mRNA encoding PDGF-A and PDGF-B (c-sis). Upon addition of the phorbol ester to the culture medium the expression of the c-sis transcript was enhanced about 7-fold over a period of 4 days. With dimethyl sulfoxide there was no significant stimulation of the expression. Addition of cycloheximide to HEL cells treated for a short period with phorbol ester superinduced the expression of the c-sis gene. The HEL cells did not express the A-chain mRNA even in the presence of phorbol ester or dimethyl sulfoxide. This leads us to propose that synthesis of the PDGF-A chain and PDGF-B chain is differentially regulated in the megakaryocytic-like HEL cell line.

Cell Differentiation↗
PubMed1987

[Significance of serum fructosamine in the metabolic control of children and adolescents with type I diabetes mellitus].

In 1982 Johnson et al. described a simple colorimetric assay for measuring glycated proteins, termed fructosamine, in the serum of adults with diabetes mellitus and demonstrated this to be a useful index of intermediate glucose control (1-3 weeks). Our study was designed to show this as well in children and adolescents with type I diabetes mellitus. Serum fructosamine was determined in 76 children and adolescents with diabetes mellitus, and 111 age-matched controls. In the controls an age-dependency but not sex-dependency could be demonstrated. In the diabetic patients we found a significant correlation between serum fructosamine and HbA1 values (r = 0.87, p less than 0.001). In 6 patients with newly diagnosed diabetes mellitus serum fructosamine concentrations decreased at a faster rate than HbA1 values. The fructosamine assay is rapid, technically simple and inexpensive, and is at least a useful addition or perhaps an alternative to HbA1 estimation.

Adolescent↗