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Biomedical subjects

T B Kardos

Publications and source records attributed to T B Kardos.

At least 19 recordsLinked to original sources

Regulation and pH-dependent expression of a bilaterally truncated yeast plasma membrane H+-ATPase.

Constitutive, chromosomal expression of yeast pma1 deletion alleles in Saccharomyces cerevisiae yielded functional, truncated forms of the plasma membrane H+-ATPase which were independently capable of supporting wild type yeast growth rates. Deletion of 27 amino-terminal residues affected neither the enzyme's activity nor its responsiveness to changes in glucose metabolism. By contrast, removal of 18 carboxy-terminal amino acids produced an enzyme with a Vmax that was relatively insensitive to glucose-dependent metabolic status and with a Km that was significantly lower than that of the wild type enzyme. These effects were exaggerated when the amino- and carboxy-terminal deletions were combined in a bilaterally truncated H+-ATPase, suggesting that the amino terminus may have a subtle role in modulating ATPase activity. In pma1DeltaDelta cells cultured at pH 6, plasma membrane H+-ATPase levels were much lower than those in cells expressing a wild type ATPase. Increased expression levels could be achieved by growing the pma1DeltaDelta mutant at pH 3, a result that was at least partially due to a sustained, elevated transcription of pma1DeltaDelta mRNA. Our observations suggest that intracellular proton balance can be maintained by regulation of the activity and/or quantity of H+-ATPase in the plasma membrane.

Amino Acid Sequence↗

A study of transposed canines in a sample of orthodontic patients.

Tooth transposition is a positional interchange of two adjacent teeth. The most commonly transposed tooth is the permanent canine with either the first premolar or lateral incisor. The records of 54 subjects with transposed canines, both maxillary and mandibular, were collected. Pretreatment study models of these subjects were matched with a similar number of models from unaffected individuals. Bucco-lingual and mesio-distal tooth widths, arch depth and arch width were measured on each model. Thirty-four subjects (63 per cent) were female. Thirty-seven (68.5 per cent) of the cases involved the maxillary arch and thirty-three (89.2 per cent) of these upper arch transpositions were of the canine and first premolar. In cases involving the lower arch the canine was invariably transposed with the lateral incisor. Peg-shaped lateral incisors, supernumerary and/or congenitally absent teeth occurred in 19 subjects. There were some small, but significant differences in the dimensions of some teeth, however there were no statistically significant differences in arch depths, arch widths and most tooth dimensions in subjects with and without transposed canines. These factors do not appear to be related to the development of canine transposition.

Anodontia↗

The effect of transforming growth factor beta one (TGF-beta 1) on wound healing, with or without barrier membranes, in a Class II furcation defect in sheep.

The purpose of this study was to analyse the effect of TFG-beta 1 on wound healing in standardized Class II furcation defects of 48 mandibular second premolar teeth in 24 sheep. The experimental design included a control group (carrier only, 25% pluronic F-127), and 2 experimental groups: group A (80 micrograms/ml TGF-beta 1 + carrier) and group B (80 micrograms/ml TGF-beta 1 + carrier covered with a barrier membrane). Sheep were killed either 2 wk or 6 wk after surgery. Mesiodistal sections of the decalcified specimens were quantified histologically using stereology. Percentage volumes of regenerated bone, fibrous connective tissue and cementum were calculated for each furcation defect. Mean values were analysed using multiple ANOVA; p values were calculated using paired and unpaired Student's t-tests. After 2 wk there was more bone in group B than either of the other 2 groups, but this was not statistically significant. By 6 wk more bone was present in group A than in the control group (p < 0.02) and also in group B when compared with both group A and the control group (p < 0.02 and p < 0.44), respectively. In the 4 wk between sampling significantly more bone had formed (group A < 0.05 and group B p < 0.003, respectively). A negative correlation existed between volumes of bone and fibrous connective tissue and no significant differences between the volumes of cementum were evident between any of the groups. This study demonstrated that TGF-beta 1 encouraged bone regeneration in Class II furcation defects in sheep, an effect enhanced by the presence of a barrier membrane. This is the first report on the use of TGF-beta 1 in conjunction with GTR in periodontal defects.

Alveolar Process↗

A comparison of stereological and computer-assisted histomorphometric analysis as tools for histological quantification in regenerative studies.

This study was designed to compare computer-assisted histomorphometric analysis (CAHA) and stereology (STER) as measurement tools for evaluating the repair response during periodontal wound healing. Thirty-six histological sections derived from 4 surgically created defects in the furcation of mandibular second premolars of sheep were measured by each technique to determine the furcation area and volume, and the percentage of new bone formation at 7 wk postoperatively. Slides were viewed in random order with the source unknown to the examiner (JL). One section from each of the 4 specimens was flagged for triplicate measurement by each technique. Intraexaminer error was determined to be low as the coefficient of variation in each of the 2 techniques was between 1% and 4%. A consistently higher percentage of bone was identified using stereology. The coefficient of agreement was plotted to determine how closely these 2 techniques were matched in their respective estimations of bone fill in a furcation defect. This analysis revealed statistical bias between the 2-techniques and a low degree of agreement between them. This study demonstrates that the 2 techniques are not interchangeable. It also emphasizes that the reader must be cautious when comparing results from studies in which different systems of measurement and analysis have been used. Stereology was determined to be the measurement tool of choice due to its high degree of reproducibility, ease of use and efficient use of time.

Animals↗

Odontoblast differentiation: a response to environmental calcium?

The response of the dental pulp to calcium hydroxide has been well described but the process of pulpal repair leading to dentinal bridge formation appears complex and the mechanisms remain incompletely understood. Through the precise regulation of the free calcium ion in the cytosol, cells have been able to utilize anions such as phosphates for a wide range of activities such as energy production (oxidative phosphorylation). As anions are abundant in the cytosol, intracellular levels of calcium ions are kept low, several orders of magnitude less than that of the surrounding extracellular matrix. Consequently, cells are able to use calcium ions for the regulation of many cellular events. The binding of extracellular molecules such as cytokines, hormones or antibodies, with receptors on the plasma membrane may result in short- or long-term modifications to cellular metabolism, including the mechanisms of intracellular calcium homeostasis. Cell survival depends upon the ability to adapt to changes in the cell's micro-environment. Adaptation in turn results in altered cellular activity that may be interpreted as showing that the cell has become more or less specialised. In some instances this may include the resumption of mitotic activity. If the rate or magnitude of change exceeds a cell's adaptive capacity, the cell dies. Responses of cells to alterations in their environment are reviewed as they may provide an explanation for the success of calcium hydroxide in facilitating pulpal repair and the differentiation of odontoblasts.

Calcium Hydroxide↗

A slow release calcium delivery system for the study of reparative dentine formation.

Several liquid, semi-solid and solid delivery systems were formulated and tested to devise a method of reproducibly administering accurate micro-doses of calcium into a 700 microns diameter cavity in a rat maxillary incisor tooth, in the absence of hydroxyl ions. Development of this delivery system was necessary to facilitate studies of the mechanisms of pulpal repair and odontoblast differentiation. The principal requirements for the delivery system were that it should be easily administered into a small pulp exposure in the rat incisor and that a greater than 1000-fold range in calcium ion concentrations could be incorporated and delivered for a period of 2-3 days, preferably in an acidic environment to minimize the effect of non-specific nucleation under alkaline conditions. Poly- (ethylene) glycol microspheres were found to be an ideal vehicle. Under the in vitro dissolution conditions used, complete release of all calcium salts occurred within 12-15 hours, except for the very water-insoluble calcium stearate. It was anticipated that the release of calcium ions would be significantly more prolonged in vivo because of the physical constraints of the prepared cavity as well as the restricted access to fluid flow.

Animals↗

In vitro characterization of poly(ethylene) glycol calcium citrate microspheres as a delivery system for the study of reparative dentinogenesis.

The characterization of poly(ethylene) glycol calcium citrate microspheres is described. The calcium content and content uniformity of microspheres, prepared at five concentrations ranging from 46.56 micrograms/g to 81.49 mg/g, were determined by spectroscopy. Under sink conditions first-order in vitro dissolution kinetics were observed. Granules containing approximately 80 mg Ca++/g PEG gave an in vitro calcium release over a 3-day period similar to that of a calcium hydroxide product, Pulpdent.

Animals↗

Functional complementation between transmembrane loops of Saccharomyces cerevisiae and Candida albicans plasma membrane H(+)-ATPases.

Saccharomyces cerevisiae PMA1 sequences encoding a putative antifungal target site comprising transmembrane loops 1 + 2 and/or 3 + 4 were replaced with the homologous sequences from Candida albicans PMA1 by using PCR-mediated domain transfer. The chimeric pma1 mutants and an isogenic wild type S. cerevisiae strain had similar growth rates, growth yields, glucose-dependent proton pumping rates, acid-activated omeprazole sensitivities, salt tolerances and antifungal sensitivities. The yields and kinetic properties of H(+)-ATPases in plasma membranes of mutant and wild type strains were comparable. Single heterologous transmembrane loops caused deleterious phenotypes at low pH and elevated temperature. Inclusion of both heterologous transmembrane loops fully suppressed the temperature sensitivity caused by heterologous transmembrane loop 1 + 2, partially suppressed the pH sensitivity and gave Candida-like in vitro sensitivity to vanadate, suggesting that the loops operate as a domain. The fully functional chimeric H(+)-ATPase containing C. albicans transmembrane loops 1 + 2 and 3 + 4 demonstrates this domain's complementarity to the equivalent region of the S. cerevisiae enzyme and validates the wild type S. cerevisiae H(+)-ATPase as an antifungal screening target.

Amino Acid Sequence↗

The mechanism of tooth eruption.

Tooth eruption is an essential process for the survival of many different species and although the movement of teeth into function has been the subject of extensive research there is no consensus as to the mechanisms involved. Recent understanding of the mechanisms of cell activation and regulation has widened the scope for further research at the molecular level. This paper reviews the evidence for an eruptive force, its direction and source. The relationships between the eruptive force and molecular mechanisms of cell activation remain to be determined.

Alveolar Process↗

Targeting the fungal plasma membrane proton pump.

The need for new mechanistic classes of broad spectrum antifungal agents has prompted development of the membrane sector and ectodomain of the plasma membrane proton pumping ATPase as an antifungal target. The fungal proton pump is a highly abundant, essential enzyme in Saccharomyces cerevisiae. It belongs to the family of P-type ATPases, a class of enzymes that includes the Na+,K(+)-ATPase and the gastric H+,K(+)-ATPase. These enzymes are cell surface therapeutic targets for the cardiac glycosides and several anti-ulcer drugs, respectively. The effects of acid-activated omeprazole show that extensive inhibition of the S. cerevisiae ATPase is fungicidal. Fungal proton pumps possess elements within their transmembrane loops that distinguish them from other P-type ATPases. These loops, such as the conformationally sensitive transmembrane loop 1+2, can attenuate the activity of the enzyme. Expression in S. cerevisiae of fully functional chimeric ATPases that contain a foreign target comprising transmembrane loops 1+2 and/or 3+4 from the fungal pathogen Candida albicans suggests that these loops operate as a domain. The chimera containing C. albicans transmembrane loops 1+2 and 3+4 provides a prototype for mutational analysis of the target region and the screening of inhibitors directed against opportunistic fungal pathogens. Panels of mutants with modified ATPase regulation or with altered cell surface cysteine residues are also described. Information about the ATPase membrane sector and ectodomain has been integrated into a model of this region.

Amino Acid Sequence↗

Immunohistochemical localisation of substance P in human parotid gland.

Based on the clinical observation that pain is experienced during parotid gland surgery under local anaesthesia, the presence of the sensory neuropeptide substance P (SP) was sought. Using a polyclonal antibody, the presence of SP was demonstrated by an indirect immunofluorescence technique, with rat parotid gland and spinal cord serving as controls. SP-containing neuronal elements occurred around acini, blood vessels and ducts. It is suggested that some of the SP-immunoreactive elements are the unmyelinated and thinly myelinated small diameter (A delta and C) fibres, which are regarded as the peripheral receptors for nociceptive information.

Adipose Tissue↗

Mucus-producing adenopapillary carcinoma of the oral cavity.

Mucus-producing adenopapillary carcinoma is a rare neoplasm of the oral cavity. The literature is reviewed and a case described, with histological and ultrastructural findings of a tumour which involved the upper lip and recurred following local excision.

Adenocarcinoma, Mucinous↗

Comparison of cryosurgery and the carbon dioxide laser in mucosal healing.

Cryosurgery is an established technique for the removal of a range of mucosal lesions. As the portable carbon dioxide laser may provide an alternative form of treatment, the effectiveness of and the healing response following use of the 2 techniques was compared by producing lesions on the lateral border of sheep tongues. Cryosurgery produced more extensive lesions with a marked inflammatory reaction but no differences in the time course of healing were evident. Laser surgery was as effective as cryosurgery in the removal of superficial tissues but caused less swelling and, therefore, may be advantageous in some clinical situations.

Animals↗

Mucosal reactions to amalgam restorations.

Amalgam restorations have been implicated both in contact sensitivity reactions and in lichenoid reactions. This appears to be related principally to the mercury content, although other metals cannot be discounted. The cases of two patients are reported who showed features of lichenoid reactions of the oral mucosa, in addition to features of a contact hypersensitivity to mercury. The mucosal lesions resolved following replacement of the amalgams with non-metallic restorations. Consideration is given to the selection of materials and procedures currently available for treatment of these patients. This paper supports the view that sensitivity to heavy metals must be considered as a possible cause of erythematous and lichenoid reactions of the oral mucosa.

Aged↗

Malignant, peripheral nerve-sheath tumour of the mandible: report of a case.

A report of an aggressive, peripheral nerve-sheath tumour that presented as a lump on the alveolar mucosa near the mental foramen is presented. Although the tumour was detected in the periphery and appeared to extend centrally, extensive surgery suggested that the tumour had its origins in the infra-temporal fossa.

Adult↗

Bacteraemia and tissue damage resulting from air polishing.

This study investigates the production of bacteraemia in dental prophylaxis by use of a commercially available air polishing device. Prophylaxis by means of the conventional rubber cup and paste method was used as a control. The study showed that air polishing can result in loss of epithelium at the gingival margin. The likelihood of a bacteraemia resulting from air polishing, in the absence of gingivitis, was less than in the group undergoing conventional prophylaxis. Although a higher number of bacteraemias was seen in the control group, the difference between the two groups was not statistically significant. Results indicate that patients who are at risk continue to require antibiotic cover.

Air↗