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Biomedical subjects

C M Allen

Publications and source records attributed to C M Allen.

At least 55 records · Page 3Linked to original sources

Ectomesenchymal chondromyxoid tumor of the anterior tongue: a report of three cases.

Ectomesenchymal chondromyxoid tumor is a newly described benign neoplasm that presents clinically as a firm, painless, slow-growing mass that typically involves the anterior dorsal tongue. It has been reported to occur over a wide age range (9 to 78 years) and has no apparent sex predilection. Histologically, the tumor is composed of a well-circumscribed, unencapsulated lobular proliferation of fusiform and polygonal cells in a chondromyxoid matrix. Features such as multilobulated nuclei, foci of cellular atypia, and infiltration may be present. Though disturbing, these do not appear to indicate malignant behavior. We report three cases of ectomesenchymal chondromyxoid tumors that confirm the previously described clinical, histologic, and immunohistochemical features. In addition, we describe the ultrastructural features of one of the cases.

Actins↗

Non-invasive screening for renal artery stenosis with ultrasound contrast enhancement.

OBJECTIVE: Our aim was to evaluate duplex ultrasound imaging in the identification of renal artery stenosis using a new technique to enhance the recorded Doppler signal. DESIGN: Colour Doppler studies of interlobar renal arteries were performed before and after enhancement using an intravenous contrast of galactose microparticle suspension containing microbubbles (Levovist, Schering) in patients with angiographically confirmed renal artery stenosis. SETTING: Blood Pressure Unit, St. George's Hospital Medical School, and Department of Radiology. The Middlesex Hospital, London, UK. PARTICIPANTS: Twenty-one consecutive hypertensive patients in whom the diagnosis of renal artery stenosis was made on digital subtraction angiography. MAIN OUTCOME MEASURES: The diagnosis of haemodynamically significant renal artery stenosis (> or = 60% on angiography). RESULTS: With Levovist, there was a 20 db increase in the Doppler intensity and, as a result, intrarenal signals were much more clearly delineated and distinct spectral waveforms were obtained from all but one kidney, which was occluded. Significant associations were found between the degree of stenosis (as assessed by angiography) and the following Doppler parameters: diastolic velocity (F = 7.6; P < 0.01), acceleration time (F = 33.5, < 0.0001), peak systolic velocity (F = 37.7, P < 0.0001) and acceleration (F = 60.0; P < 0.0001). Without enhancement, there were five false-positive and two false-negative examinations (sensitivity 85%; specificity 79%) using the acceleration cut-off value of 3.5 m/s2 to identify haemodynamically significant renal artery stenosis (> or = 60% on angiography). After contrast enhancement, there were only three false-positive and one false-negative examinations (sensitivity 94% and specificity of 88%) using the acceleration cut-off value of 3.75 m/s2 and the examination time was reduced by approximately half (sensitivity and specificity of 90% using the acceleration cut-off value of 3.5 m/s2). CONCLUSIONS: Our results suggest that renal duplex scanning using contrast enhancement is a promising new non-invasive technique in screening patients with suspected renal artery stenosis. Contrast enhancement produces more reproducible spectral waveforms, improves accuracy and halves the examination time.

Adult↗

Photoreactive analogues of prenyl diphosphates as inhibitors and probes of human protein farnesyltransferase and geranylgeranyltransferase type I.

Photoreactive analogues of prenyl diphosphates have been useful in studying prenyltransferases. The effectiveness of analogues with different chain lengths as probes of recombinant human protein prenyltransferases is established here. A putative geranylgeranyl diphosphate analogue, 2-diazo-3,3,3-trifluoropropionyloxy-farnesyl diphosphate (DATFP-FPP), was the best inhibitor of both protein farnesyltransferase (PFT) and protein geranylgeranyltransferase-I (PFFT-I). Shorter photoreactive isprenyl diphosphate analogues with geranyl and dimethylallyl moieties and the DATFP-derivative of farnesyl monophosphate were much poorer inhibitors. DATFP-FPP was a competitive inhibitor of both PFT and PGGT-I with Ki values of 100 and 18 nM, respectively. [32P]DATFP-FPP specifically photoradiolabelled the beta-subunits of both PFT and PGGT-I. Photoradiolabelling of PGGT-I was inhibited more effectively by geranylgeranyl diphosphate than farnesyl diphosphate, whereas photoradiolabelling of PFT was inhibited better by farnesyl diphosphate than geranylgeranyl diphosphate. These results lead to the conclusions that DATFP-FPP is an effective probe of the prenyl diphosphate binding domains of PFT and PGGT-I. Furthermore, the beta-subunits of protein prenyltransferases must contribute significantly to the recognition and binding of the isoprenoid substrate.

Affinity Labels↗

Changes in protein prenylation and prenyltransferase activity in the rat seminiferous epithelium during early stages of spermatogenesis.

Changes in protein prenyltransferase activity, levels of prenylated protein, and the type of isoprenoid modification was described in cells of rat seminifereous epithelium and correlated with differentiative events of spermatogenesis. The activity of protein farnesyltransferase (PFT) was at least 10-fold higher than that for protein geranylgeranyltransferase-I (PGGT-I) in seminiferous epithelium and spermatogenic cells of prepubertal rats of different ages. Both activities increased during the meiotic stages of differentiation and peaked at 23 days of age. The activity of farnesyltransferase in seminiferous epithelium was the same as that in mixed spermatogenic cell populations from animals aged 9 and 23 days, indicating that the activity of this enzyme in somatic cells and germ cells was similar at these ages. Farnesyltransferase activities were similar and low in both pachytene spermatocytes and round spermatids from adult rats; however, the activity in pachytene spermatocytes from 23-day old animals was 2-fold higher than in adults. The highest activity was associated with intermediate-sized spermatocytes appearing late during meiosis. PGGT-I activity was at least 10-fold lower than farnesyltransferase activity and was not significantly different among all cell populations. Differentiation-dependent in vivo protein prenylation was demonstrated by labeling of seminiferous epithelium with [3H]mevalonic acid at different prepubertal ages. Total protein prenylation and the ratio of geranylgeranylated to farnesylated protein, in contrast to prenyltransferase activity, decreased with increasing age. Although 20-30-kDa proteins were the most highly labeled at all ages, [3H]-proteins from different-aged prepubertal rats showed age-dependent changes in the level of prenylation of at least 14 proteins as determined by two-dimensional (2D) electrophoresis. Prenylated proteins of round spermatids were distinguished from those of the spermatocytes by the lack of many 20-30-kDa proteins and by low geranylgeranyl/farnesyl (GG/F) ratios. These results show that independent changes in prenyltransferase activity and protein prenylation accompany the differentiation events during the premeiotic and meiotic stages of spermatogenesis. This suggests that prenylation in the seminiferous epithelium may be more dependent on available protein substrate than on protein prenyltransferase activity.

Aging↗

Sulfophthalocyanines for photodynamic inactivation of viruses in blood products: effect of structural modifications.

Transmission of infectious disease through blood transfusions is well known. Ultraviolet irradiation, solvents, and detergents provide a means of sterilizing noncellular blood components. However, these harsh methods are not applicable to cellular blood products. Recently, attempts have been made to sterilize biological fluids using photodynamic treatment and phthalocyanine (Pc) dyes have been advanced as photosensitizers for this purpose. We have evaluated a series of water-soluble Pc, chelated with different central metal ions, substituted to different degrees with sulfonato and t-butyl groups, for their effectiveness to reduce virus infectivity in red blood cell suspensions. Vaccinia virus cytopathogenicity was determined by endpoint serial dilutions in the CV-1 cell line. Anti-viral activity increased with the central metal ion in the following: Ga(III) < Al(III) < Zn(II), and varied inversely with the degree of sulfonation. Furthermore, addition of a t-butyl group onto the trisulfonated dyes (PcS3[t-Bu]) resulted in a 5-40-fold increase in anti-viral potency, suggesting that amphiphilicity enhances the photodynamic activity of the dye. Strong anti-viral photosensitizing properties cannot be the sole selection criterion. Of equal importance is the preservation of blood component integrity. Accordingly, the photohemolytic activity of the dyes was evaluated using the rate of hemolysis as a parameter and a toxicity index was defined. Among the most active dyes, the AlPcS3(t-Bu) complex exhibited the most favorable anti-viral properties combined with a low toxicity index. Our results suggest that trisulfophthalocyanines, bearing an additional t-butyl group to enhance amphiphilicity, are particularly promising dyes for photodynamic blood sterilization.

Animals↗

Humoral hypercalcemia of malignancy associated with ameloblastoma in a horse.

Humoral hypercalcemia of malignancy was evident in a horse that had a locally invasive ameloblastoma of the left hemimandible. Surgical removal of the neoplasm resulted in prompt return of serum calcium and parathyroid hormone concentrations to within reference limits. The tumor contained parathyroid hormone-related protein, as demonstrated by immunohistochemistry and western blot analysis. It is likely that production of this protein by the neoplasm was important in the pathogenesis of the hypercalcemia. The case represented a sporadic form of humoral hypercalcemia of malignancy attributable to an uncommon epithelial neoplasm, and indicated that humoral hypercalcemia of malignancy can develop with neoplasms in horses.

Ameloblastoma↗

Necrosis in benign salivary gland neoplasms. Not necessarily a sign of malignant transformation.

Necrosis that occurs in a salivary gland neoplasm is usually considered to be an ominous sign, suggesting malignant transformation, particularly in lesions that have had no prior manipulation such as fine-needle aspiration. We describe five pleomorphic adenomas and two canalicular adenomas of salivary gland origin that exhibited necrosis, yet were otherwise benign. All lesions displayed a distinctive histopathologic pattern characterized by a narrow rim of viable tumor tissue at the periphery of the neoplasm combined with a diffuse central region that demonstrated apparent ischemic necrosis. No invasion of adjacent normal tissue was identified, and no recurrence or metastasis has been seen with these lesions. Caution should be exercised in the evaluation of salivary gland neoplasms with central necrosis to avoid misdiagnosis of all such lesions as malignant.

Adenoma↗

Animal models of oral candidiasis. A review.

Candida albicans is the most common fungal infection of the human oral mucosa, yet much remains to be understood with respect to the pathogenesis of the disease. Numerous difficulties are inherent in designing studies that use human beings as subjects. The use of various animal species in experimental contexts has helped to provide insight with respect to this condition. A variety of manipulations of the system can be performed, including altering the host immune response, the mucosal environment, or the systemic environment. In addition, organism-related factors can be examined in a more controlled setting. The information obtained from such studies could not be obtained in an in vitro situation.

Anemia↗

Adult rhabdomyoma. A light microscopic, ultrastructural, virologic, and immunologic analysis.

Adult rhabdomyoma is a rare benign tumor of skeletal muscle origin that frequently arises from musculature of the head and neck region. In this study we report five cases of adult rhabdomyoma. Light and electron microscopic examination revealed the typical cellular features as described by others. The results of immunophenotyping and quantitation of nucleolar organizer regions were consistent for a benign skeletal muscle tumor. Epstein-Barr virus and human papillomavirus genomic DNA could not be detected by in situ hybridization.

Actins↗