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Biomedical subjects

C M Allen

Publications and source records attributed to C M Allen.

At least 19 recordsLinked to original sources
PubMed2001

Modification of Rab5 with a photoactivatable analog of geranylgeranyl diphosphate.

A photoprobe analog of geranylgeranyl diphosphate (2-diazo-3,3,3-trifluoropropionyloxy-farnesyl diphosphate or DATFP-FPP) inhibits mevalonate-dependent prenylation of in vitro translated Rab5 in rabbit reticulocyte lysate, suggesting that it competes for lipid binding to the Rab geranylgeranyl transferase. Modification of Rab5 with DATFP-FPP, demonstrated by gel mobility shift and Triton X-114 phase separation experiments, confirms that the enzyme uses the analog as a substrate. The sedimentation of DATFP-modified Rab5 as a larger mass complex on sucrose density gradients indicates that it binds to other factors in rabbit reticulocyte lysate. Most importantly, DATFP-Rab5 cross-links to these soluble factors upon exposure to UV light. Immunoprecipitation with antibodies raised against proteins known to interact with Rab5 reveals that the cross-linked complexes contain Rab escort protein and GDI-1. DATFP-Rab5 also associates with membranes in a guanosine-5'-O-(3-thiotriphosphate)-stimulated manner. However, although prenylated Rab5 can be cross-linked to two unknown membrane-associated factors by the chemical cross-linker disuccinimidyl suberate, these proteins fail to be UV cross-linked to membrane-bound DATFP-Rab5. These results strongly suggest that membrane-associated factors bind Rab5 through protein-protein interactions rather than protein-prenyl interactions. The modification of Rab5 with DATFP-FPP establishes a novel photoaffinity technique for the characterization of prenyl-binding sites.

Animals↗
PubMed2001

The association between Viadent use and oral leukoplakia.

Recently, leukoplakia of the maxillary vestibule was described in patients with no traditional risk factors but who had used Viadent products. We designed a case-control study to evaluate the hypothesis that Viadent users were more likely to have lesions. One hundred and forty-eight cases and controls were identified through the Section of Oral and Maxillofacial Pathology. Cases and controls were administered a questionnaire about Viadent use and other known risks. Results of crude, stratified, and logistic regression analyses showed that use of Viadent products was a risk indicator for leukoplakia (adjusted OR = 9.7, 95% CI = 4.7-21.6), with a strong dose-response relation.

Alcohol Drinking↗
PubMed2000

Enhanced prenyltransferase activity and Rab content in rat liver regeneration.

Rabs are small GTP-binding proteins with a regulatory role in intracellular vesicular traffic. The modulation of their levels and activity in different physiological situations is poorly understood. During the first cell cycle of rat liver regeneration we observed a differential regulation of some Rabs, with a progressive increase of those involved in exocytosis and a progressive decrease of one involved in endocytosis. This could be related with the need of exposing growth factor receptors and prolonging the transduction of their signal in preparation for mitosis. Moreover, we observed an increased activity of protein prenyltransferases, the enzymes responsible for the prenylation of several proteins involved in crucial processes of proliferation, without a corresponding increase in the amount of prenyltransferase protein.

Animals↗
PubMed2000

Angiosarcoma of the mandible: a case report and review of the literature.

Angiosarcoma is a rare malignancy that is characterized by endothelial cell differentiation. In the head and neck area, most of these lesions arise in the scalps of elderly individuals. Less commonly, angiosarcomas can be found within bone. The purpose of this report is to describe an example of angiosarcoma involving the floor of the mouth and right body of the mandible. The histopathologic and immunopathologic features of these lesions are also reviewed.

Aged↗
PubMed2000

[Hybrid 3D visualization and virtual endoscopy in cochlear implants].

PURPOSE: The aim of this study was to demonstrate on a complex anatomical structure the possibilities and the advantages of a superimposition of a color-coded surface and volume rendering (hybrid rendering) method with the possibility of the performance of a virtual endoscopy. MATERIAL AND METHOD: In 6 patients with cochlear implants a high-resolution spiral computed tomography of the petrous bone was performed. The cochlear implants, the middle and inner ear structures were visualized using a color-coded surface rendering method, either shaded or as a grid. The petrous bone was visualized using a transparent volume rendering method. RESULTS: The hybrid 3D visualization uses the advantages of both the color-coded 3D surface and volume rendering method. In comparison to the axial source images, the hybrid 3D visualization thus facilitates a clearer representation and better assessment of the complex topographical relationship without loss of diagnostic information. The virtual endoscopy facilitates an intraluminal visualization and inspection of all color-coded 3D surface- and volume rendered structures. CONCLUSIONS: The hybrid rendering and virtual endoscopy make the morphological assessment of cochlear implants easier by the simultaneous visualization of the surrounding structures and thereby support the diagnostic imaging methods. This image processing method can be used pre-operatively for the individual planning, simulation, training and further development of surgical procedures and interventions and post-operatively for the control of the position and further developments of implants.

Adolescent↗
PubMed2000

Paraneoplastic pemphigus: a review of the literature.

Paraneoplastic pemphigus is a relatively rare but highly significant acquired mucocutaneous disorder. The condition typically presents in patients with previously diagnosed lymphoreticular disease, primarily malignancies (non-Hodgkin's lymphoma; chronic lymphocytic leukemia). Multiple sites of involvement are common, with the skin affected by a polymorphous eruption that includes lichenoid plaques as well as bullae. The oral lesions occur in all cases and present as painful widespread shallow ulcers with hemorrhagic crusting of the lips. Conjunctival involvement is also seen and may result in scarring. Pulmonary lesions are an ominous sign. Histopathologically, intraepithelial and subepithelial clefting associated with interface dermatitis are seen. A variety of autoantibodies directed against desmoplakins and desmogleins can be identified with immunoprecipitation studies. Treatment with immunosuppressive agents may result in some resolution of the disease, but the prognosis for paraneoplastic pemphigus is considered to be poor.

Autoantibodies↗
PubMed1999

Evaluation of the middle and inner ear structures: comparison of hybrid rendering, virtual endoscopy and axial 2D source images.

Recent developments in 3D reconstructions can enhance the quality and diagnostic value of axial 2D image data sets with direct benefits for clinical practice. To show the possible advantages of a hybrid rendering method [color-coded 3D shaded-surface display (SSD)- and volume rendering method] with the possibility of virtual endoscopy we have specifically highlighted the use in relation to the middle and inner ear structures. We examined 12 patients with both normal findings and postoperative changes, using image data sets from high-resolution spiral computed tomography (HRSCT). The middle and inner ear was segmented using an interactive threshold interval density volume-growing method and visualized with a color-coded SSD rendering method. The temporal bone was visualized using a transparent volume rendering method. The 3D- and virtual reconstructions were compared with the axial 2D source images. The evaluated middle and inner ear structures could be seen in their complete form and correct topographical relationship, and the 3D- and virtual reconstructions indicated an improved representation and spatial orientation of these structures. A hybrid and virtual endoscopic method could add information and improve the value of imaging in the diagnosis and management of patients with middle or inner ear diseases making the understanding and interpretation of axial 2D CT image data sets easier. The introduction of an improved rendering algorithm aids radiological diagnostics, medical education, surgical planning, surgical training, and postoperative assessment.

Adult↗
PubMed1999

Referral patterns, lesion prevalence, and patient care parameters in a clinical oral pathology practice.

OBJECTIVE: The purpose of this study was to determine the following parameters in a referral-based private practice oral and maxillofacial pathology clinic: (1) sources of clinical referrals; (2) types of problems referred; and (3) clinical effectiveness of treatment. STUDY DESIGN: Clinical charts were reviewed for a cohort of 362 patients seen over a 2 1/2-year period (1993-1995). From these charts, we determined the source of referral and the final diagnosis for each patient. In addition, 50 patients were randomly selected and surveyed by telephone; each was asked a series of questions to determine the following: (1) the number of health care practitioners previously seen with regard to the patient's condition; (2) the length of time that the condition had been present before the patient came to the oral and maxillofacial pathology clinic; (3) the costs associated with medications and office visits that had been incurred before the patient came to the oral and maxillofacial pathology clinic; (4) the costs associated with medications and office visits that were incurred at the oral and maxillofacial pathology clinic; and (5) the patient's level of satisfaction with the oral and maxillofacial pathology clinic. RESULTS: Fifty-five percent of the referrals came from dentists, and 45% came from physicians. The 3 problems most commonly seen were candidiasis (12%), burning mouth syndrome (10%), and lichen planus (8%). For the 50 patients who were interviewed, the mean number of health care practitioners seen previously was 2.2 (range, 1-9). The mean time from initial symptoms to evaluation by an oral pathologist was 15 months. The mean approximate cost of medications and office visits before evaluation by an oral pathologist was $350 (range, $30-$4,000; median, $100); this compared with a cost of $94 (range, $50-$300; median, $70) for the patient visit and medications associated with the oral pathology appointment. The difference was statistically significant (P < or = .001). CONCLUSIONS: This preliminary study suggests that the clinical evaluation of oral lesions by an oral pathologist appears to be cost-effective and should be an integral part of a comprehensive health management system. These results should be corroborated by similar multicenter studies.

Adolescent↗
PubMed1999

Photodynamic therapy: tumor targeting with adenoviral proteins.

A brief summary of the mechanisms involved in photodynamic therapy (PDT) and the role of delivery vehicles for photosensitizer targeting is addressed. Phthalocyanines (Pc) have been coupled to adenovirus type 2 capsid proteins including the hexon, the penton base and the fiber to enhance their target selectivity. Adenovirus penton base proteins contain the arginine-glycine-aspartic acid peptidic sequence (RGD) motif known to bind with great affinity and high specificity to integrin receptors, expressed by several types of cancer. Tetrasulfonated aluminum phthalocyanine (AlPcS4) was covalently coupled to the various capsid proteins via one or two caproic acid spacer chains (A1 or A2) in 7:1 up to 66:1 molar ratios. The capacity of the bioconjugates for singlet oxygen production, as measured by an L-tryptophan oxidation assay, was strongly reduced, likely reflecting scavenging by the carrier. Cell adsorption and in vitro photocytotoxicity assays were carried out using the A549 and HEp2 human cell lines expressing integrin receptors, and one murine, the EMT-6 cell line, which lacks receptors for the RGD sequence. The AlPcS4A2-protein complexes induced greater cytotoxicity as compared to the analogous AlPcS4A1 preparations. The penton base-AlPcS4A2 derivative was the more phototoxic for all cell lines tested. Tumor response studies using Balb/c mice with EMT-6 tumor implants demonstrated that the free AlPcS4A2 induced complete tumor regression at a dose of 1 mumol/kg and 400 J/cm2, which is comparable to the activity of the known AlPcS2adj. A mixture of adenovirus type 2 soluble proteins covalently labeled with AlPcS4A2 required 0.5 mumol/kg to induce the same response with the same light dose, suggesting that the high affinity RGD/receptor complex is able to target Pc for PDT.

Animals↗
PubMed1998

Hybrid rendering and virtual endoscopy of the auditory and vestibular system.

A hybrid rendering method (color-coded 3D shaded-surface and volume display) with the possibility of virtual endoscopy using image data sets from HR-SCT was developed. To show the possible advantages and benefits of the improved rendering algorithm we have specifically highlighted the use in relation to the auditory and vestibular system. Postprocessing image visualization offers improved morphological analysis, and will benefit radiological diagnostics, medical education, surgical planning, surgical training and postoperative assessment.

Adult↗
PubMed1998

Estrogen stimulates intracellular traffic in the liver of Rana esculenta complex by modifying Rab protein content.

During vitellogenesis in oviparous animals, estrogens induce the synthesis of the yolk precursor vitellogenin, a lipophosphoprotein rich in cholesterol. Estrogens also induce the activity of 3-hydroxy-3-methylglutaryl CoA reductase, that is necessary for the lipidation of vitellogenin. This increased enzyme activity could also be important for the production of isoprenoid groups that post-translationally modify proteins such as the Rab proteins, which are small G proteins involved in intracellular traffic. The effect of estrogens on the production of prenylated proteins and on the levels of Rab proteins in the liver of Rana esculenta complex has been studied. An increase of the Rabs specifically involved in the exocytic pathway was observed and is probably related to the need for export of massive amounts of newly synthesized vitellogenin.

Animals↗
PubMed1998

Protein prenyl transferase activities of Plasmodium falciparum.

Prenylated proteins have been shown to function in important cellular regulatory processes including signal transduction. The enzymes involved in protein prenylation, farnesyl transferase and geranylgeranyl transferase, have been recent targets for development of cancer chemotherapeutics. We have initiated a systematic study of protein prenyl transferases of the malaria parasite, Plasmodium falciparum, to determine whether these enzymes can be developed as targets for antimalarial chemotherapy. We report here the identification of protein farnesyl transferase and protein geranylgeranyl transferase-I in the malaria parasite, P. falciparum. The farnesyl transferase has been partially purified from the cytosolic fraction through ammonium sulfate precipitation and Mono-Q chromatography. Farnesyl and geranylgeranyl transferase-I activities are present at all stages of P. falciparum intraerythrocytic development with maximum specific activity in the ring stage. Geranylgeranyl transferase-I specific activity is two times that of farnesyl transferase in the ring stage. Peptidomimetics and prenyl analogues of protein farnesyl transferase substrates were tested as in vitro inhibitors of partially purified P. falciparum prenyl transferase and of malaria parasite growth. The peptidomimetics were significantly more potent inhibitors than lipid substrate analogues of both the activity of Mono-Q purified enzyme and parasite growth in intraerythrocytic cultures. Exposure of the parasite to the peptidomimetic L-745,631 also showed significant inhibition of morphological development beyond the trophozoite stage. These studies suggest the potential of designing or identifying differential inhibitors of P. falciparum and mammalian prenyl transferases as an approach to novel malaria therapy.

Alkyl and Aryl Transferases↗