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Biomedical subjects

D Keller

Publications and source records attributed to D Keller.

At least 37 records · Page 2Linked to original sources
PubMed1999

MDM2 suppresses p73 function without promoting p73 degradation.

The newly identified p53 homolog p73 can mimic the transcriptional activation function of p53. We investigated whether p73, like p53, participates in an autoregulatory feedback loop with MDM2. p73 bound to MDM2 both in vivo and in vitro. Wild-type but not mutant MDM2, expressed in human p53 null osteosarcoma Saos-2 cells, inhibited p73- and p53-dependent transcription driven by the MDM2 promoter-derived p53RE motif as measured in transient-transfection and chloramphenicol acetyltransferase assays and also inhibited p73-induced apoptosis in p53-null human lung adenocarcinoma H1299 cells. MDM2 did not promote the degradation of p73 but instead disrupted the interaction of p73, but not of p53, with p300/CBP by competing with p73 for binding to the p300/CBP N terminus. Both p73alpha and p73beta stimulated the expression of the endogenous MDM2 protein. Hence, MDM2 is transcriptionally activated by p73 and, in turn, negatively regulates the function of this activator through a mechanism distinct from that used for p53 inactivation.

Apoptosis↗
PubMed1999

Where to treat? Is the habitual bite the best functional bite relationship?

One important consideration for any dental treatment involves evaluating the relationship of the mandible to the maxilla. Is the habitual bite that the patient possesses the best functional bite? There are a multiplicity of factors that must be considered in this evaluation before the doctor determines whether to treat to the patient's habitual bite position, or should a better bite position be determined.

Biomechanical Phenomena↗
PubMed1998

Characterization of a novel structural member, LukE-LukD, of the bi-component staphylococcal leucotoxins family.

A new member of the staphylococcal bi-component leucotoxins family, LukE (32 kDa) and LukD (34.3 kDa) has been characterized from Staphylococcus aureus strain Newman. LukE was 58-68% identical with the class S proteins, whereas LukD was 71-77% identical with the class F proteins of the family. A partial immunoreactivity with the various affinity-purified antibodies specific for the other proteins was observed. Immunoprecipitation assay and gene probing confirmed a 30% frequency among human clinical isolates, differing from the distribution of the other known leucotoxins (P<0.005). LukE+LukD was as effective as the Panton-Valentine leucocidin for inducing dermonecrosis when injected in the rabbit skin, but not hemolytic and poorly leucotoxic compared to other leucotoxins expressed by Staphylococcus aureus.

Amino Acid Sequence↗
PubMed1997

Utilization of recombinant adenovirus and dominant negative mutants to characterize hepatocyte nuclear factor 4-regulated apolipoprotein AI and CIII expression.

Using recombinant adenoviral vectors and a dominant negative mutant of HNF-4, we have examined the contribution of hepatocyte nuclear factor 4 (HNF-4) to endogenous apolipoprotein AI and CIII mRNA expression. Overexpression of HNF-4 leads to a 7.4-fold increase in apolipoprotein CIII expression, while infection with the dominant negative mutant of HNF-4 reduces the level of apolipoprotein CIII mRNA by 80%, demonstrating that endogenous HNF-4 is necessary for apolipoprotein CIII expression. Experiments using the hepatoma cell lines, HepG2 and Hep3B, indicate that HNF-4 is also involved in the regulation of apolipoprotein AI expression in these lines. However, the effect of HNF-4 on apolipoprotein AI expression is much more dramatic in cell lines derived from intestinal epithelium. Infection of the intestinal-derived cell line IEC-6 with the HNF-4 adenovirus resulted in a greater than 20-fold increase in the level of apolipoprotein AI mRNA. These results indicate that HNF-4 does regulate apolipoprotein AI and CIII mRNA expression and suggest that HNF-4 is critical for intestinal apolipoprotein AI expression.

Adenoviridae↗
PubMed1997

Ela 1.0--a framework for life-cycle impact assessment developed by the Fraunhofer-Gesellschaft. Part A: The conceptual framework.

The Fraunhofer-Gesellschaft has sponsored the development of a conceptual and flexible, computer aided tool to perform the impact assessment within LCA (life cycle assessment) for technical products and processes. The developed general framework "Ela 1.0" (environmental loads analysis) consists of four elements: the selection of appropriate impact categories, the categorization of emissions and wastes leaving the systems as well as of resource and energy consumption, the characterization and an analysis of the results of the impact assessment. The latter compares the product-based emissions with the total of emissions of a region such as Germany, the EU or OECD countries. The framework Ela 1.0 considers the environmental categories: global warming, ozone depletion, resource and energy consumption, wastes, eutrophication (including COD and BOD as measured parameters), acidification, ecotoxicity, ozone formation and human toxicity. The latter categories are handled by listing of precursors for ozone formation, and by listing of emissions scored according to their human hazard potential. The options, possibilities and limitations of the conceptual framework are presented in part A of a series of publications.

Acid Rain↗
PubMed1996

Thresholds for tactile sensitivity perceived with dental implants remain unchanged during a healing phase of 3 months.

The aim of the present study was to determine the tactile pressure thresholds perceived with dental implants during a three-month healing phase following implant placement (osseointegration phase). The absolute threshold of tactile perception was measured in a group of patients 1 week, 1, 2 and 3 months following implant placement (ITI Dental Implant System, Straumann AG, Waldenburg, Switzerland). Contralateral and neighbouring teeth were measured at the same time. For determination of the axial forces exerted on the implants and teeth, and electronic device with semi-conductor strain gauges was used (Hämmerle et al. 1995). The results demonstrated mean thresholds of tactile perception for the implants of 160.2 g (SD 61.7 g, range 77 approximately 283 g) at 1 week, 133.4 g (SD 51.9 g, range 32 approximately 239 g) at 1 month, 147.9 g (SD 53.5 g, range 70 approximately 257 g) at 2 months, and 146.9 g (SD 57.4 g, range 77 approximately 248 g) at 3 months. Statistical analysis using Student's paired t-test revealed no significant differences between the values over time. The control teeth exhibited mean values for tactile perception of 13.1 g (SD 9.6 g, range 5 approximately 47 g) at 1 week, 10.2 g (SD 6.4 g, range 4 approximately 29 g) at 1 month, 14.8 g (SD 15.9 g, range 2 approximately 58 g) at 2 months, and 15.4 g (SD 12.2 g, range 3 approximately 36 g) at 3 months. Again, these values did not differ significantly from each other and indicated the absence of systemic alterations in perceived pressure threshold over the observation period. The mean perceived pressure threshold was more than 10 times higher for implants than for natural teeth (P < 0.001) at all observation times. It is concluded that the absolute threshold of tactile perception with dental implants during the phase of osseointegration is not affected by bone and soft tissue healing taking place during the time period.

Adult↗
PubMed1994

Safety and immunogenicity of a recombinant outer surface protein A Lyme vaccine.

OBJECTIVE: To evaluate the safety and immunogenicity of a recombinant outer surface lipoprotein A (OspA) Lyme vaccine in healthy adults. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Clinical research unit of a medical center. PARTICIPANTS: Thirty-six healthy adult volunteers aged 18 through 65 years. INTERVENTIONS: Volunteers were randomly assigned to receive two 10-micrograms doses of OspA Lyme vaccine, OspA Lyme vaccine adsorbed to alum, or a buffer placebo. Subjects in the OspA Lyme vaccine group received a third dose. Patients were assessed after each vaccination for a total follow-up period of 1 year. Serum samples for antibody determination were drawn at baseline, 2 and 3 weeks after dose 1, once per week for 4 weeks after dose 2, 20 weeks after dose 2, and 1 month after dose 3. MAIN OUTCOME MEASURES: Local and systemic adverse reactions and antibody levels specific for OspA. RESULTS: The most common reactions were local pain and tenderness at the injection site. Adverse events did not increase following the second or third dose. Two doses of both vaccine formulations elicited high-titer antibodies that inhibited replication of Borrelia burgdorferi in vitro. No differences were noted in antibody levels elicited by the adsorbed and nonadsorbed formulations. CONCLUSION: Two or three doses of OspA Lyme vaccine are safe and immunogenic in adults.

Adolescent↗
PubMed1993

Comparative effects of in vivo treatment using interleukin-11 and stem cell factor on reconstitution in mice after bone marrow transplantation.

Molecular analysis of the hematopoietic microenvironment (HM) has led to the characterization and molecular cloning of two unique growth factors produced by stromal cells. Interleukin (IL)-11 and stem-cell factor (SCF; steel factor [SF]) have been shown in a variety of in vitro culture systems to stimulate distinct populations of stem, progenitor, and more differentiated cell types. We have analyzed and compared the effects of each growth factor administered to mice undergoing bone marrow transplantation (BMT) after total body irradiation (TBI). We report that IL-11 stimulates platelet and neutrophil recovery, while the main effect of SCF is on erythroid cell recovery in this model. Mice treated with the combination of IL-11 and SCF show increases in all three lineages compared with control mice, without obvious toxicity. In addition, both the type of progenitor- and stem-cell populations stimulated and the anatomic localization of effects seen with each growth factor are distinct. These data in mice suggest that the combination of IL-11 and SCF might be useful in humans undergoing myeloablative therapies.

Animals↗
PubMed1993

Cytoskeleton of living, unstained cells imaged by scanning force microscopy.

Subsurface cytoskeletal structure can be visualized in either fixed or living mammalian cells in aqueous medium with approximately 50 nm resolution using the Scanning Force Microscope (SFM). In living cells, changes in cell topography, or subsurface cytoskeleton caused by the introduction of drugs (colchicine) or cross-linking of surface receptors (by antibodies against IgE bound to the IgE receptor) can be followed in time. Contrast in SFM images of cell surfaces result from both topographic features of the cell and from variations in cell surface "stiffness". The SFM is therefore capable of measuring local compliance and stress in living cells, and so should make it possible to map the cytoskeletal forces used to generate cell motions and changes in cell shape.

Animals↗
PubMed1993

Retreating orthodontic failures: Part I.

This article presents a number of cases originally treated by orthodontic specialists which were retreated because the initial results became unstable over time. Diagnostic evaluations uncovered many common reasons for the initial treatment failures. Methods utilized during re-treatment addressed the causative factors related to the initial instability and have proven effective in maintaining a consistent dental relationship for over five years. The results have been both aesthetic and functional.

Humans↗
PubMed1993

Retreating orthodontic failures: Part II.

Part I of this series (June 1993 JGO) clearly documented the inadequacies of some orthodontic methods to obtain satisfactory stable results for patients. Forty-four patients were selected for this study, as their prior orthodontic treatments--all from orthodontic specialists or orthodontic postgraduate institutions--had failed for a variety of functional reasons. The treatment for the 44 patients would not have been necessary if the initial orthodontic treatment had been successful. Therefore, somewhere in the treatment, problems existed which were not corrected by the treatment methods, or problems arose because of the treatment methods. Part I of this series clearly and precisely showed that some orthodontic methods initiate TMJ problems. In a review of the literature presented in Part I, the following conclusions were reached: 1. The optimum functional relationship of the human temporomandibular joint exists when the force vectors within the joint are directed anteriorly and superiorly. 2. Some orthodontic treatments disrupt this optimum functional relationship by placing posterior or posterior/superior forces on the structures of the temporomandibular joint. 3. There is an increased incidence of joint signs and symptoms for some of the patients treated with those conventional methods which place pathologic forces on the temporomandibular joints. Present treatment methods are inadequate if they damage the patient's structures. The guidelines of treatment are wrong if problems exist because of the treatment methods and these guidelines then need to be corrected. What is offered in this article is a method of treatment that was and is successful in retreating those patients who were initially treated by orthodontic specialists, yet who developed TMJD problems during or after their treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Dental Occlusion, Centric↗
PubMed1992

Substrate preparation for reliable imaging of DNA molecules with the scanning force microscope.

A simple method of substrate preparation for imaging circular DNA molecules with the scanning force microscope (SFM) is presented. These biomolecules are adsorbed onto mica that has been soaked in magnesium acetate, sonicated and glow-discharged. The stylus-sample forces that may be endured before sample damage occurs depends on the ambient relative humidity. Images of circular DNA molecules have been obtained routinely using tips specially modified by an electron beam with a radius of curvature, Rc, of about 10 nm [D. Keller and C. Chih-Chung, Surf. Sci. 268 (1992) 333]. The resolution of these adsorbed biomolecules is determined by the Rc. At higher forces individual circular DNA molecules can be manipulated with the SFM stylus. Strategies to develop still sharper probes will be discussed.

Aluminum Silicates↗
PubMed1991

Relative and combined effects of heat and noise exposure on sleep in humans.

In a counter-balanced design, the effects of daytime and/or nighttime exposure to heat and/or traffic noise on night sleep were studied in eight healthy young men. During the day, the subjects were exposed to baseline condition (ambient temperature = 20 degrees C; no noise) or to both heat (35 degrees C) and noise. The duration of the daytime exposure was 8 h ending 5 h before sleep onset. The following nights, the subjects slept either in undisturbed (20 degrees C; no noise) or in noise, heat, or noise plus heat-disturbed environments. During the day, the various types of traffic noise were distributed at a rate of 48/h with peak intensities ranging between 79 and 86 dB(A). The background noise level was at 45 dB(A). At night, the peak intensities were reduced by 15 dB(A), the rate was diminished to 9/h, and the background noise was at 30 dB(A). Electrophysiological measures of sleep and esophageal and mean skin temperatures were continuously recorded. The results showed that both objective and subjective measures of sleep were more disturbed by heat than by noise. The thermal load had a larger impact on sleep quality than on sleep architecture. In the nocturnal hot condition, total sleep time decreased while duration of wakefulness, number of sleep stage changes, stage 1 episodes, number of awakenings, and transitions toward waking increased. An increase in the frequency of transient activation phases was also found in slow-wave sleep and in stage 2. In the nocturnal noise condition, only total number of sleep stage changes, changes to waking, and number of stage 1 episodes increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Human IgE-binding protein: a soluble lectin exhibiting a highly conserved interspecies sequence and differential recognition of IgE glycoforms.

IgE-binding protein (epsilon BP) refers to a protein originally identified in rat basophilic leukemia cells by virtue of its affinity for IgE. It is now known to be a beta-galactoside-binding lectin equivalent to carbohydrate-binding protein 35 (CBP 35). More recently, its identity to Mac-2, a macrophage cell-surface protein, has been established. cDNA coding for human epsilon BP has been cloned from a human HeLa cell cDNA library and contains an open reading frame of 750 base pairs encoding a 250 amino acid protein. Like the rat and murine counterparts, the human epsilon BP amino acid sequence can be divided into two domains with the amino-terminal domain consisting of a highly conserved repetitive sequence (YPGXXXPGA) and the carboxyl-terminal domain containing sequences shared by other S-type lectins. The human epsilon BP sequence exhibits extensive homology to murine and rat epsilon BP with 84% and 82% identity, respectively. The homology is particularly striking in the carboxyl-terminal domain where 95% identity is found between human and murine sequences in a stretch of over 70 amino acids. A survey of epsilon BP mRNA expression from several lymphocyte cell lines revealed that the level of epsilon BP transcription may reflect a relationship between cell differentiation and epsilon BP expression. Finally, human epsilon BP was purified from several human cell lines and shown to possess lactose-binding characteristics and cross-species reactivity to murine IgE. Surprisingly, three different human myeloma IgE proteins did not show reactivity to human epsilon BP. However, after neuraminidase treatment of each human IgE, pronounced binding to epsilon BP was observed, thereby indicating that only specific IgE glycoforms can be recognized by epsilon BP.

Amino Acid Sequence↗
PubMed1989

Imaging of metal-coated biological samples by scanning tunneling microscopy.

A method for imaging biological samples by scanning tunneling microscopy (STM) is presented. There are two main difficulties in imaging biological samples by STM: (1) the low conductivity of biological material and (2) finding a method of reliably depositing the sample on a flat conducting surface. The first of these difficulties was solved by coating the samples with a thin film of platinum-carbon. The deposition problem was solved by a method similar to a procedure used to deposit biological molecules onto field ion microscope (FIM) tips. STM images of bacteriophage T7 and filamentous phage fd are shown. The substrate on which the samples were absorbed was atomically flat gold. The images do not show molecular detail due to the metal coating, but the gross dimensions and morphology are correct for each type of virus. Also, the surface density of virus particles increases and decreases in the way expected when the conditions of deposition are changed. These methods allow reliable and reproducible STM imaging of biological samples.

Bacteriophages↗
PubMed1989

Imaging of single uncoated DNA molecules by scanning tunneling microscopy.

Scanning tunneling microscope images of DNA molecules absorbed onto highly oriented pyrolytic graphite have been obtained. Three methods of deposition and sample preparation have been utilized. In the first method, a highly concentrated solution of DNA is sonicated, and a drop is deposited on freshly cleaved graphite. Under these conditions, the molecules tend to align in a parallel fashion, forming liquid-crystalline phases. In the second method, a solution of DNA is deposited directly on the graphite surface without sonication. In this case, ammonium acetate, a volatile salt, is used to decrease the amount of the residual salt crystals left after drying. In the third method, a solution containing lysed phage particles and DNA is adsorbed onto a graphite surface. The molecules are seen either isolated or in small bundles. The values of height, periodicity, and thickness observed and the handedness of the molecules are consistent with those expected for DNA. In all cases, the molecules were identified by their characteristic periodic structure and because, at higher magnification, no graphite-like structure was detectable on the surface of the molecules. Often the DNA molecules appear to adsorb in areas of the graphite that have many steps and defects. A mechanism that explains the magnitude of the tunneling currents measured in DNA is proposed. This mechanism, in turn, suggests a general method by which large insulating molecules can be rendered conductive.

DNA↗