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Biomedical subjects

M Sarikaya

Publications and source records attributed to M Sarikaya.

At least 19 recordsLinked to original sources

Regulated gene expression dictates enamel structure and tooth function.

Enamel is a complex bioceramic tissue. In its final form, enamel is a reflection of the unique molecular and cellular activities occurring during organogenesis. From the ectodermal origins of ameloblasts, their gene activity and protein expression profiles exist for the sole purpose of producing a mineralized shell, almost entirely devoid of protein, deposited over the 'bone-like' dentine. The interface between enamel and dentine is referred to as the dentine enamel junction and it is also unique in its biology. This review article is narrow in its scope. We restrict our review to selected advances in our understanding of the genetic, molecular and structural aspects of enamel biology. We present a model of enamel formation that relates gene expression to the assembly of an extracellular protein matrix that in turn controls the structural hierarchy and mechanical aspects of enamel and the tooth organ.

Amelogenin↗

Biological organization of hydroxyapatite crystallites into a fibrous continuum toughens and controls anisotropy in human enamel.

Enamel forms the outer surface of teeth, which are of complex shape and are loaded in a multitude of ways during function. Enamel has previously been assumed to be formed from discrete rods and to be markedly aniostropic, but marked anisotropy might be expected to lead to frequent fracture. Since frequent fracture is not observed, we measured enamel organization using histology, imaging, and fracture mechanics modalities, and compared enamel with crystalline hydroxyapatite (Hap), its major component. Enamel was approximately three times tougher than geologic Hap, demonstrating the critical importance of biological manufacturing. Only modest levels of enamel anisotropy were discerned; rather, our measurements suggest that enamel is a composite ceramic with the crystallites oriented in a complex three-dimensional continuum. Geologic apatite crystals are much harder than enamel, suggesting that inclusion of biological contaminants, such as protein, influences the properties of enamel. Based on our findings, we propose a new structural model.

Anisotropy↗

A genetic analysis of crystal growth.

The regulation of crystal morphology by proteins is often observed in biology. It is a central feature in the formation of hard tissues such as bones, teeth and mollusc shells. We have developed a genetic system in the bacterium Escherichia coli to study the protein-mediated control of crystal growth. We have used the crystallization of gold as a model system and found polypeptides that control the morphology of the resulting gold crystals. Analysis of the crystallization process influenced by these polypeptides indicates they act catalytically by an acid mechanism. Our results suggest that the concepts and methods of microbial genetics are general and can be applied to substances not commonly found in biological systems.

Acids↗

Enamel biomineralization defects result from alterations to amelogenin self-assembly.

Enamel formation is a powerful model for the study of biomineralization. A key feature common to all biomineralizing systems is their dependency upon the biosynthesis of an extracellular organic matrix that is competent to direct the formation of the subsequent mineral phase. The major organic component of forming mouse enamel is the 180-amino-acid amelogenin protein (M180), whose ability to undergo self-assembly is believed to contribute to biomineralization of vertebrate enamel. Two recently defined domains (A and B) within amelogenin appear essential for this self-assembly. The significance of these two domains has been demonstrated previously by the yeast two-hybrid system, atomic force microscopy, and dynamic light scattering. Transgenic animals were used to test the hypothesis that the self-assembly domains identified with in vitro model systems also operate in vivo. Transgenic animals bearing either a domain-A-deleted or domain-B-deleted amelogenin transgene expressed the altered amelogenin exclusively in ameloblasts. This altered amelogenin participates in the formation an organic enamel extracellular matrix and, in turn, this matrix is defective in its ability to direct enamel mineralization. At the nanoscale level, the forming matrix adjacent to the secretory face of the ameloblast shows alteration in the size of the amelogenin nanospheres for either transgenic animal line. At the mesoscale level of enamel structural hierarchy, 6-week-old enamel exhibits defects in enamel rod organization due to perturbed organization of the precursor organic matrix. These studies reflect the critical dependency of amelogenin self-assembly in forming a competent enamel organic matrix and that alterations to the matrix are reflected as defects in the structural organization of enamel.

Amelogenesis↗

Chemical peritonitis associated with high dialysate acetaldehyde concentrations.

BACKGROUND: During the standard heat sterilization process of lactate-buffered peritoneal dialysis (PD) solutions, glucose degrades to form compounds called glucose degradation products such as acetaldehyde, formaldehyde, or glyoxal. Despite evidence that these products may be responsible for some in vitro cytotoxic effects induced by commercially available PD fluids, data on their acute or chronic effects on the human peritoneum is scarce. SUBJECTS AND METHODS: This case presentation is based on an observation of 21 aseptic peritonitis cases of unknown aetiology. All cases appeared within one month in a university hospital PD unit that had a peritonitis rate of 1 episode/26 patient months and 55 active patients on CAPD. Acetaldehyde level in the bags was assayed by gas chromatography. RESULTS: Twenty-one patients presented with signs of peritonitis including cloudy dialysate and abdominal tenderness with additional abdominal pain in 11 patients and vomiting in one. In all cases, cultures and Gram stains were negative for micro-organisms. Fever was not observed in any patient. Average dialysate white blood cell count was 1795/mm(3). All patients were free of intraperitoneal medication when symptoms appeared. Patients were using PD solutions from a newly established domestic production plant. Apparently all patients with symptoms of peritonitis used bags with the same lot number and the solution in the bags appeared to be darker in colour than that in bags with other lot numbers. Chemical analysis of the unused PD solution samples revealed acetaldehyde levels of 17-20 p.p. m. in bags containing darker solution, which is very high compared with the usual acetaldehyde level of 6 p.p.m. in heat-sterilized PD solutions. CONCLUSIONS: Based on the above findings, we hypothesize that higher levels of acetaldehyde and possibly other glucose degradation products may have been an aetiological factor in these 21 cases of chemical peritonitis. Our observation suggests that acetaldehyde, in concentrations 3-4 times higher than the usual level in commercially available PD solutions, may induce acute sterile peritonitis in CAPD patients.

Acetaldehyde↗

Spin-stretching of DNA and protein molecules for detection by fluorescence and atomic force microscopy.

We have developed a rapid and efficient way of stretching DNA and denatured protein molecules for detection by fluorescence microscopy and atomic force microscopy (AFM). In the described method, a viscous drag created by transient rotational flow stretches randomly coiled DNA molecules or denatured proteins. Stretching is achieved by dispensing a droplet of sample solution containing DNA or denatured protein on a MgCl2-soaked mica surface. We present fluorescent images of straightened lambdaDNA molecules and AFM images of stress-shared, reduced von Willebrand factor as well as straightened lambdaDNA. The described quick and reliable spin-stretching technique will find wide applications in the analysis of single biopolymer molecules.

DNA↗

Sharp DNA bends as landmarks of protein-binding sites on straightened DNA.

We have developed a fluorescence-based method for mapping single or multiple protein-binding sites on straightened, large-size DNA molecules (> 5 kbp). In the described method, protein-DNA complexes were straightened and immobilized on a flat surface using surface tension. A fraction of the immobilized complexes displayed a sharp DNA bend with two DNA segments extending from the apex. The presence of DNA-binding proteins at the apex was verified by atomic force microscopy. The position of protein binding relative to the ends of the DNA molecule was determined by measuring the length of two DNA segments using fluorescence microscopy. We demonstrate the potential of the fluorescence-based method to localize protein-binding sites on the DNA template and to evaluate relative binding affinity. The proposed protein-binding-site mapping technique is simple and easy to perform. Practical applications include screening for DNA-binding proteins and the localization of protein-binding sites on large segments of DNA.

Bacteriophage lambda↗

Low-loss Electron Energy-loss Spectroscopy and Dielectric Function of Biological and Geological Polymorphs of CaCO(3).

: Previous work on microstructural characterization has shown variations in terms of defects and organization of nanostructures in the two polymorphs of calcium carbonate, calcite, and aragonite in mollusc shells. Large variations in mechanical properties are observed between these sections which have been attributed to variations in composite microstructure as well as intrinsic properties of the inorganic phases. Here we present local low-loss electron energy-loss spectroscopic (EELS) study of calcitic and aragonitic regions of abalone shell that were compared to geological (single-crystal) counterpart polymorphs to reveal intrinsic differences that could be related to organismal effects in biomineralization. In both sets of samples, local dielectric function is computed using Kramer-Kronig analysis. The electronic structures of biogenic and geological calcitic materials are not significantly different. On the other hand, electronic structure of biogenic aragonite is remarkably different from that of geological aragonite. This difference is attributed to the increased contribution from single electron excitations in biogenic aragonite as compared to that of geological aragonite. Furthermore, an apparent bound characteristic of the Re(1/epsilon) is observed for biological samples which suggests a "quasi-plasmon"-like nature of the collective excitations. Implications of these changes are discussed in the context of macromolecular involvement in the making of the microstructures and properties in biogenic phases.

Journal Article↗

Response to triple treatment with omeprazole, amoxicillin, and clarithromycin for Helicobacter pylori infections in continuous ambulatory peritoneal dialysis patients.

In this study, the response to triple treatment with omeprazole, amoxicillin, and clarithromycin was investigated in continuous ambulatory peritoneal dialysis (CAPD) patients with Helicobacter pylori (Hp) infections. The study enrolled 20 CAPD patients (11 male, 9 female) who had dyspeptic complaints. The mean age of the patients was 46 (range: 21-65). The study also enrolled, as a control group, 124 patients (66 male, 58 female) who had no systemic disease, but who had upper gastrointestinal endoscopy for dyspeptic complaints. The mean age of the patients in the control group was 47 years (range: 20-74 years). Upper gastrointestinal endoscopy, rapid urease test (CLO test), and direct histologic examination were carried out to detect Hp infection. Hp infection was detected in 10 cases (50%) in the CAPD group and in 53 cases (43%) in the control group. In both groups, patients with Hp infection received the triple treatment of omeprazole 20 mg twice daily for 30 days, amoxicillin 500 mg thrice daily for 15 days, and clarithromycin 500 mg thrice daily for 15 days. To assess response to treatment, upper gastrointestinal endoscopy, CLO test, and direct histologic examination were repeated 3 months after initiation of the treatment. Hp was eradicated in all of the 11 CAPD patients (100%), and in 42 of the control patients (92%). Our results suggest that the triple treatment with omeprazole, amoxicillin, and clarithromycin for Hp infection is as effective in CAPD patients as in the normal population.

Adult↗

Neural network model of on-off units in the fly visual system: simulations of dynamic behavior.

We analyze the dynamic properties of a neural network model for on-off spiking neurons recorded in the first optic chiasm of the fly visual system. The model consists of two parallel pathways and three sequential processing stages. The first stage models photoreceptors. At the second stage, the signal is segregated into on- and off-pathways. These pathways are proposed to correspond to two populations of amacrine cells. At the third stage, the on- and off-pathways converge to on-off neurons. Furthermore, according to the model, on-off neurons interact via recurrent connections. This stage is proposed to correspond to lamina L4 neurons. In response to luminance increments and decrements, the model exhibits a three-component response and suggests pathways for each of the components. When stimulated by a train of pulses, the model exhibits fast adaptation for frequencies higher than about 5 Hz. Furthermore, adaptation to on- and off-pulses occurs independently. When the frequency of stimulation is reduced, the unit recovers rapidly from its adapted state. The temporal modulation transfer function has its peak around 7 Hz. The phase characteristics show a phase lead for low temporal frequencies changing to a phase lag for high frequencies. These model predictions are compared with data from Jansonius and van Hateren (1991).

Adaptation, Physiological↗

An introduction to biomimetics: a structural viewpoint.

Biomimetics is a newly emerging interdisciplinary field in materials science and engineering and biology in which lessons learned from biology form the basis for novel technological materials. It involves investigation of both structures and physical functions of biological composites of engineering interest with the goal of designing and synthesizing new and improved materials. This paper discusses microarchitectural aspects of some structural biocomposites, presents microstructural criteria for future materials design and processing, and identifies areas of future research.

Animals↗