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Biomedical subjects

M Toner

Publications and source records attributed to M Toner.

At least 19 recordsLinked to original sources

Multiple teeth showing invasive cervical resorption--an entity with little known histologic features.

Invasive cervical resorption is a relatively uncommon form of external root resorption, characterized by resorption of the cervical region of the root. There is progressive loss of cementum and dentine with replacement by fibrovascular tissue derived from the periodontal ligament, with deposition of cementum-like hard tissue. In most cases, a single tooth is involved. We report a case of invasive cervical resorption that resulted in loss of multiple teeth from two different quadrants. The case highlights the diagnostic difficulty that may arise in this uncommon lesion, the pathologic features of which may be mistaken for a fibro-osseous lesion or a low-grade sarcoma.

Adult↗

Squamous cell carcinoma of the head and neck in young Irish adults.

Classically, squamous cell carcinoma (SCC) of the head and neck is a disease of older adults, but recently there have been reports of an increasing incidence in young people. This study of patients in the Republic of Ireland compares sex distribution, sites, risk factors, stage and grade of tumour, and nodal status of 130 patients with SCC of the head and neck, 30 of whom were less than 40 years old. There was a highly significant association between age, smoking status, and site of tumour. For the first time to our knowledge in a study such as this, the preoperative haematological status of the patients was assessed, and although 15% were anaemic there was no significant difference in the occurrence of anaemia between the younger and the older patients. We think that it is possible that the biology of SCC of the head and neck in young people differs from that in older people.

Adolescent↗

Histological evidence for lichen planus in clinically normal perilesional tissue.

The objective of this study was to examine the histological features of apparently normal oral mucous membrane adjacent to lesions of oral lichen planus. Twenty-six patients attending an oral medicine unit with clinical lesions typical of oral lichen planus had biopsies of lesional and perilesional sites. Biopsies were examined for histopathological features of oral lichen planus. Twenty-two (85%) of lesional biopsies and 12 (46%) of the perilesional biopsies were reported as either typical or showing some features of lichen planus. Twelve of these 22 cases (55%) had both lesional and perilesional biopsies reported as either typical or showing some features of lichen planus. These 12 cases represented 46% of all cases. In four cases (15%) neither the lesional nor the adjacent perilesional biopsy was reported as lichen planus. The inflammatory process in oral lichen planus may extend beyond the confines of the clinical lesion into adjacent mucous membrane of normal appearance.

Adult↗

Necrotizing sialometaplasia: an unusual bilateral presentation associated with antecedent anaesthesia and lack of response to intralesional steroids. Case report and review of the literature.

Necrotizing sialometaplasia is a self-limiting, variably ulcerated benign process affecting minor salivary glands. Accurate histological diagnosis is paramount, as it has been mistaken for malignancy, which has resulted in excessively aggressive and unnecessary radical surgery. A unique case of bilateral necrotizing sialometaplasia, presenting with anaesthesia of the greater palatine nerves, is described. An attempt at active therapy with intralesional steroids had no effect on the course of the condition.

Adult↗

Hyalinizing clear cell carcinoma of salivary gland: an aggressive variant.

Although hyalinizing clear cell carcinoma (HCCC) had been previously illustrated by several authors, it was not until 1994 that this tumour was characterized by Milchgrub et al. [Am J Surg Pathol (1994),18,74] and separated from the heterogeneous group of clear cell carcinomas described in the literature. HCCC is a distinctive infiltrative low-grade, monomorphic, glycogen-rich clear cell carcinoma with prominent stromal hyalinization occurring most often in the minor salivary glands of adult women. A case of hyalinizing clear cell carcinoma arising in the tongue of an adult female is described with special reference to the presence of minor foci of mitotic activity, necrosis and anaplasia in this otherwise typical low-grade carcinoma. Widespread metastases and death within a year of initial presentation in this case suggests that there may be a subset of this indolent tumour in which these features are associated with a poor prognosis.

Adenocarcinoma, Clear Cell↗

British Society for Oral and Maxillofacial Pathology, UK: minimum curriculum in oral pathology.

This paper describes a minimum curriculum in oral pathology for undergraduate dental education in the United Kingdom prepared by the Teachers Group of The British Society of Oral and Maxillofacial Pathology. Curricular development in UK dental schools is overseen by the General Dental Council (GDC), the Quality Assurance Agency for Higher Education (QAA) and the European Union. These organisations define the framework for education and learning outcomes but provide little or no detailed guidance on syllabus or curriculum. This recommended minimum curriculum has been drawn up by a consensus process involving teachers of oral pathology from all 13 UK and one Irish dental schools and is cross-referenced to the GDC and QAA published requirements for undergraduate dental education.

Curriculum↗

Tensile strength, histological and immunohistochemical observations of periodontal wound healing in the dog.

This study was designed to study wound strength at the dentine/connective tissue interface and at the bone/connective tissue interface following full thickness flap surgery. Flaps of uniform dimension were outlined in four young adult beagle dogs using a standardised double bladed knife and vertical incisions 10 mm apart, which extended 8 mm apical to the gingival margin. Bone was removed from half the sites (eight sites in each dog), giving 32 flaps replaced on dentine and 32 sites on bone. A tensile force was applied using a microprocessor force gauge at 1, 2, 3, 7, 10, 14, 21, and 28 days. Mean tensile strengths were markedly weaker for the dentine/flap interface. At 7 days the value for flaps to dentine was 1.82 N, in contrast to 5.08 N for flaps replaced on bone. Inflammatory cell counts tended to fall markedly at 3 days for both modalities, but were higher for the dentine/flap modality at all time points. Fibroblast density peaked at 7-14 days but did not vary with type of flap over the time points studied. The amounts of fibrin were greater for the dentine/flap interface at all time points but decreased for both flap types as time progressed. Collagen type V was localised to the basement membrane and blood vessels and tended to show more foci for flaps replaced on dentine. Procollagen levels showed little change over the healing interval for both flap/bone and flap/dentine interfaces. Type III collagen synthesis was at peak levels during the first week. These findings would support efforts to stabilise periodontal flaps at early time points, especially those on dentine.

Alveolar Process↗

Osseous malignant non-Hodgkin's B-cell lymphoma associated with total hip replacement.

We report a case of non-Hodgkin B-cell lymphoma within the bony base of an implanted acetabular cup of a total hip arthroplasty. The diagnosis was made while revising a loose prosthesis and treatment of a non-union of a periprosthetic fracture. This case demonstrates that it is important to consider tumour development in differential diagnoses of pain originating in and around a loose prosthesis. It also illustrates the need for better understanding of the relationship between haematopoietic malignancies and possible carcinogenic effects of implant debris.

Aged↗

Telomerase activity detected in oral lichen planus by RNA in situ hybridisation: not a marker for malignant transformation.

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory condition. Clinically, it is characterised by the presence of a white lace-like lesion on the buccal mucosa, tongue, and gingivae, with erosions and ulceration. The World Health Organisation considers OLP to be a premalignant condition. AIMS: To investigate expression of the telomerase RNA component (hTR) in OLP compared with normal control buccal mucosa and to assess the possibility of using hTR expression as a marker for malignant transformation in OLP. METHODS: hTR expression was analysed in 40 cases of OLP and 18 normal control buccal mucosa samples using an RNA in situ hybridisation approach. RESULTS: Strong hTR RNA expression was seen in the basal, suprabasal, and to a lesser extent in the upper epithelial layers in 36 of the 40 OLP lesions examined. Infiltrating subepithelial lymphocytes in OLP were also shown to express hTR RNA. Weak hTR RNA expression was seen in seven of the 18 normal control buccal mucosa specimens, with expression confined exclusively to the basal layer of the epithelium and absent in the suprabasal and upper layers. CONCLUSION: The telomerase RNA component hTR is found to be highly expressed in the epithelium of non-dysplastic OLP lesions. It is possible that this high expression is related to the increased cellular proliferation seen in OLP lesions rather than being an indicator of susceptibility to malignancy. Thus, hTR RNA expression may not be a suitable marker for predicting malignant transformation in OLP.

Adult↗

Critical issues in bioartificial liver development.

End-stage liver disease accounts for over 30,000 deaths annually in the United States. Orthotopic liver transplantation is the only clinically proven treatment for patients with end-stage liver failure. A limitation of this therapy is a shortage of donor organs available. This donor organ shortage is exacerbated by the fact that the number of patients listed for transplantation has continued to increase. As a result, there has been a continuing increase in the number of patients who die waiting for a donor liver. Extracorporeal bioartificial liver devices consisting of viable hepatocytes have the potential to provide temporary support for patients with fulminant hepatic failure, thereby serving as a "bridge" to transplantation. In some patients, this temporary support would allow the native liver to regenerate function, eliminating the need for transplantation and the resulting life-long immunosuppressive therapy, all of which translates into a cost savings to the health care system. Although the bioartificial liver device is a promising technology for the treatment of liver failure, significant technical challenges remain in order to develop systems with sufficient processing capacity and of manageable size. An overview of the critical issues in the development of bioartificial liver devices is discussed.

Animals↗

Effects of oxygenation and flow on the viability and function of rat hepatocytes cocultured in a microchannel flat-plate bioreactor.

The goal of this study was to investigate the viability and synthetic function of rat hepatocytes cocultured with 3T3-J2 fibroblasts in a small-scale microchannel flat-plate bioreactor with and without an internal membrane oxygenator under flow. Bioreactor channel heights ranged between 85 and 500 microm and medium flow rates ranged between 0.06 and 4.18 mL/min. The results showed that the bioreactor without the oxygenator resulted in significantly decreased viability and function of hepatocytes, whereas hepatocytes in the bioreactor with internal membrane oxygenator were able to maintain their viability and function. The shear stress calculations showed that, at lower wall shear stresses (0.01 to 0.33 dyn/cm(2)), hepatocyte functions, measured as albumin and urea synthesis rates, were as much as 2.6- and 1.9-fold greater, respectively, than those at higher wall shear stresses (5 to 21 dyn/cm(2)). Stable albumin and urea synthesis rates for 10 days of perfusion were also demonstrated in the bioreactor with internal membrane oxygenator. These results are relevant in the design of hepatocyte bioreactors and the eventual scaling-up to clinical devices.

3T3 Cells↗

Starfish oocytes form intracellular ice at unusually high temperatures.

Starfish oocytes, eggs, and embryos are popular models for studying meiotic maturation, fertilization, and embryonic development. Their large (170- to 200-microm) oocytes are obtainable in copious amounts and are amenable to manipulations that mammalian oocytes are not. The most formidable obstacle to working with marine oocytes is their seasonal availability, yet a successful means of preserving them for use during the nonreproductive season has not been reported. The aim of this study was to investigate the response of starfish oocytes to freezing with rapid and slow cooling rates under a variety of conditions to develop a cryopreservation protocol for these cells. Cryomicroscopic observation revealed that starfish oocytes in isotonic medium undergo intracellular ice formation (IIF) at very high subzero temperatures, such that the mean difference between the temperature of extracellular ice formation (T(EIF)) and IIF (TI(IF)) was less than 3 degrees C and the average T(IIF) was approximately between -4 and -6 degrees C. Neither partial cellular dehydration nor addition of the cryopreservative dimethyl sulfoxide significantly depressed the T(IIF). Under some conditions, we observed ice nucleation at multiple locations within the cytoplasm, suggesting that several factors contribute to the unusually high T(IIF) during controlled-rate freezing and thus vitrification may be a more suitable method for cryopreserving these cells.

Animals↗

Beneficial effect of intracellular trehalose on the membrane integrity of dried mammalian cells.

Recently, there has been much interest in using trehalose and other small carbohydrates to preserve mammalian cells in the dried state as an alternative to cryopreservation. Here, we report on the successful preservation of plasma membrane integrity after drying, as a first step toward full preservation of mammalian cells. Trehalose was introduced into cells using a genetically engineered version of alpha-hemolysin, a pore-forming protein; the cells were then dried and stored for weeks at different temperatures with approximately 90% recovery of the intact plasma membrane. We show that protection of the plasma membrane by internal trehalose is dose dependent and estimate the amount of internal trehalose required for adequate protection to be approximately 10(10) molecules/cell. In addition, a minimal amount of water (approximately 15 wt%) appears to be necessary. These results show that a key component of mammalian cells can be preserved in a dried state for weeks under mild conditions (-20 degrees C and 5% relative humidity) and thereby suggest new approaches to preserving mammalian cells.

3T3 Cells↗

Poloxamer-188 improves capillary blood flow and tissue viability in a cutaneous burn wound.

After cutaneous burn injury, an area of tissue 1-2 mm thick surrounding the wound is the site of a pronounced inflammatory response where blood flow is reduced. This "zone of stasis" undergoes progressive necrosis within 24-48 h, resulting in an expansion of the burn wound. Poloxamer-188 (P-188) is a surfactant that has been shown to prevent cell death due to electrical injury in vivo and heat shock in vitro. In this study, we investigated the effect of P-188 on blood flow within and around a burn wound and on the expansion of the wound area within 24 h after administration of a full-thickness burn injury. Results show that immediately (0-2 h) after the burn, red blood cell speed decreased to zero in a zone extending up to 1 mm from the center of the burn in both P-188 (200 mg/kg)- and saline (0.9%)-treated animals. Between 1 and 3 mm from the center of the burn, red blood cell speed decreased to 50% of preburn levels in saline controls (n = 5), while no decrease occurred in P-188-treated animals (n = 5). Beyond 3 mm from the center of the burn, red blood speed was equal to the preburn levels in saline controls, while it increased by about 10% in P-188 animals. Twenty-four hours after administration of burn, the "zero red blood cell speed zone," termed as the zone of coagulation, became smaller in P-188-treated animals, with an area of 2.4 +/- 0.5 mm(2) (n = 5) compared to 3.5 +/- 0.5 mm(2) (n = 4) in saline controls (P < 0.01). These results suggest that P-188 prevented the formation of a zone of stasis within 2 h after the burn injury and reduced the area of coagulation observed 24 h after cutaneous burn injury.

Animals↗

Holding forces of single-particle dielectrophoretic traps.

We present experimental results and modeling on the efficacy of dielectrophoresis-based single-particle traps. Dielectrophoretic forces, caused by the interaction of nonuniform electric fields with objects, have been used to make planar quadrupole traps that can trap single beads. A simple experimental protocol was then used to measure how well the traps could hold beads against destabilizing fluid flows. These were compared with predictions from modeling and found to be in close agreement, allowing the determination of sub-piconewton forces. This not only validates our ability to model dielectrophoretic forces in these traps but also gives insight into the physical behavior of particles in dielectrophoresis-based traps. Anomalous frequency effects, not explainable by dielectrophoretic forces alone, were also encountered and attributed to electrohydrodynamic flows. Such knowledge can now be used to design traps for cell-based applications.

Biophysical Phenomena↗

A fulminant hepatic failure model in the rat: involvement of interleukin-1beta and tumor necrosis factor-alpha.

The development of a fulminant hepatic failure (FHF) model is necessary for evaluating the efficacy of extracorporeal liver support systems. Recognizing the multifaceted functions of the liver, including synthesis and degradation, we investigated blood chemistry, histological findings, and survival rate in D-galactosamine (GalN)-intoxicated rats. The pathophysiologic response of inflammatory cytokines, interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), was also measured. Sprague-Dawley rats (200-300 g) were divided into two groups: GalN and saline injection. Rats were killed at 1, 3, 6, 12, 24, 36, 48, 72, and 168 hr after intraperitoneal injection of GalN (1.4 g/kg) or saline. In both groups, liver-specific markers, liver histology, and IL-1beta and TNF-alpha levels in blood and liver tissue were analyzed. In a second series of experiments, the survival rates were examined after two administrations of GalN at 1.0, 1.4 or 2.0 g/kg, at a 12-hr interval. In the GalN injection group, the liver-specific markers reached peak levels between 36 and 48 hr after injection. Histologically, hepatocellular necrosis was seen at 6-48 hr, followed by a regenerative phase occurring between 72 and 168 hr. IL-1beta and TNF-alpha levels in liver tissue peaked at 12 hr and 1 hr, respectively. The levels of these cytokines in blood, however, did not change significantly. The survival rates at day 7 for 1.0, 1.4 or 2.0 g/kg GalN injected twice were 77.8%, 16.7%, and 0%, respectively. These results suggest that single and double injection of GalN enable the development of reversible and irreversible FHF models. The results also indicate that IL-1beta and TNF-alpha are useful markers of liver injury.

Animals↗

In vitro and in vivo evaluation of albumin synthesis rate of porcine hepatocytes in a flat-plate bioreactor.

Several configurations of extracorporeal bioartificial liver devices have been developed for the potential treatment of fulminant hepatic failure or as a bridge to liver transplantation. Recently, we developed a microchannel flat-plate bioreactor with an internal membrane oxygenator in which porcine hepatocytes are cultured as a monolayer on the bottom glass surface. In the present study, we investigated synthetic function of porcine hepatocytes in the bioreactor in both in vitro and in vivo flow circuit models. In vitro, albumin synthesis was stable in the bioreactor for up to 4 days of perfusion. In vivo, with the extracorporeal connection of the bioreactor to rat vasculature, porcine albumin was detectable for 24 h in the rat plasma. We also developed a simple mathematical model to predict the in vivo porcine albumin concentration in rat plasma. These results indicate that this configuration of a microchannel flat-plate bioreactor has potential as a liver support device and warrants further investigation.

Albumins↗