bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of a spiny plant refuge in structuring grazed shortgrass steppe plant communities
Authors: Rebollo S. , Milchunas D. G. , Noy‐Meir I. , Chapman P. L.
Published: March 2003

This study evaluates the hypothesis that biological grazing refuges have an important role in plant‐grazer interactions of grasslands with a long history of grazing. We assessed the hypothesis that clumps of the spiny cactusOpuntia polyacanthaprovide biological refuges from cattle grazing, affecting cover and seedhead production of associated vascular plants in the shortgrass steppe of the North America. The study was based on sampling inside and outsideOpuntiaclumps in eight long‐term moderately grazed pastures established 60 yr ago and their respective ungrazed controls.Opuntiaclumps provided a refuge for seedhead production of the dominant grass (Bouteloua gracilis) and for cover and seedhead production of many plant groups. Clumps were also a refuge for species sensitive to grazing (species that decrease with grazing) and barrel‐cacti, but not for species preferred by cattle (species with greater proportion in the diet than in the field), exotics or weeds. Our results suggest that these effects were mainly through changes in the microenvironmental conditions resulting from protection effects, even though all potential microenvironmental effects could not be measured. Cacti promoted some negative effects on other plant groups, probably due to the space occupied by cladodes inside cactus clumps. The refuge effects observed at the group level did not translate into strong community level effects. Species diversity (H′) was greater in cactus clumps due to lower dominance rather than greater richness. The presence ofOpuntiaclumps increased landscape‐scale diversity. This ecological role ofOpuntiaclumps as refuge from cattle grazing should be taken into consideration in management practices aimed at cactus eradication in order to increase forage availability for livestock. We discuss the potential role of plant community productivity and grazing history with regard to the importance of natural refuges in structuring grassland communities.
Simultaneous occurrence of lymphoepithelial cysts, cytomegalovirus and mycobacterial infections in the intraparotid lymph nodes of a patient with AIDS
Authors: Vargas P. A. , Villalba H. , Passos A. P. , Saldiva P. H. N. , Mauad T. , Filho H. H. Caiaffa , Lucena A. , Almeida O. P.
Published: March 2003

Abstract: We report the unusual simultaneous occurrence of lymphoepithelial cysts, cytomegalovirus (CMV) and mycobacterial infections in the intraparotid lymph nodes of a 52‐year‐old AIDS patient who died of disseminated mycobacteriosis. Although cytomegalovirosis is a common finding in the salivary glands of HIV patients, the association of CMV inclusions with lymphoepithelial cyst (LC) has not been previously reported. Parotid mycobacterial infection is an uncommon finding, despite its usual disseminated presentation in HIV patients. These data emphasize that in immunosuppressed patients, simultaneous diseases of the parotid gland may occur and should be considered for diagnosis and treatment.
Oral mucosal lesions and risk habits among men in an Italian study population
Authors: Campisi G. , Margiotta V.
Published: March 2003

Abstract: A randomly selected study population of 118 male subjects (≥40 years) living on the Mediterranean island of Pantelleria (southwest of Sicily, Italy) was examined for the presence of oral mucosal lesions, with particular emphasis on the early diagnosis of oral precancerous and cancerous lesions. The study population was interviewed for socioeconomic and behavioural information, and clinically examined using WHO criteria. The prevalence of oral mucosal lesions observed, and data obtained about oral hygiene, tobacco smoking, alcohol drinking and exposure to actinic radiation, were analysed. Alcohol drinking was the most common habit in the study population (73%), followed by tobacco smoking (58.5%, of whom 96% were cigarette smokers). Only 3% showed good oral hygiene and 25% were edentate. Oral lesions were observed in 81.3% of the study group, mainly coated tongue (51.4%), leukoplakia (13.8%), traumatic oral lesions (traumatic ulcers and frictional white lesions) in 9.2%, actinic cheilitis (4.6%), and squamous cell carcinoma in one case (0.9%). Statistically significant associations were found between the prevalence of coated tongue and tobacco smoking (P<0.0001), and between the prevalence of actinic cheilitis and tobacco smoking/alcohol drinking (P<0.05). Analysis of clinical and anamnestic data underlined the effective presence, in the population examined, of the behavioural risk factors for oral precancerous and cancerous lesions, and the lack of cultural motivation towards primary prevention activities, such as the elimination of risk habits.
Immunohistochemical detection of hepatocyte growth factor, transforming growth factor‐β and their receptors in epithelial odontogenic tumors
Authors: Kumamoto Hiroyuki , Yoshida Mitsuhide , Ooya Kiyoshi
Published: March 2003

Background:   Tumors derived from odontogenic epithelium exhibit considerable variation and are classified into several benign and malignant entities. To clarify the role of growth factors in oncogenesis, cytodifferentiation and progression of epithelial odontogenic tumors, expression of hepatocyte growth factor (HGF), transforming growth factor‐β (TGF‐β) and their receptors were analyzed in these tumors as well as in tooth germs.

Methods:   Specimens of five tooth germs, 34 ameloblastomas, three calcifying epithelial odontogenic tumors (CEOTs), two clear cell odontogenic tumors (CCOTs), five adenomatoid odontogenic tumors (AOTs), six calcifying odontogenic cysts (COCs) and six malignant ameloblastomas were examined immunohistochemically with the use of antibodies against HGF, TGF‐β and their receptors.

Results:   In tooth germs and epithelial odontogenic tumors, immunoreactivity for HGF and TGF‐β was detected in both epithelial and mesenchymal cells, while expression of their receptors was found only in epithelial cells. In tooth germs and main types of ameloblastomas, HGF and TGF‐β reactivity was marked in epithelial cells near the basement membrane, and their receptors were diffusely positive in most epithelial cells. In subtypes of ameloblastomas, reduced expression of HGF, c‐Met and TGF‐β and increased reactivity for TGF‐β receptors were detected in keratinizing cells in acanthomatous ameloblastomas, and granular cells in granular cell ameloblastomas demonstrated little or no expression of HGF, TGF‐β or their receptors. As compared with main types of ameloblastomas, basal cell ameloblastomas showed high HGF reactivity, and desmoplastic ameloblastomas exhibited elevated reactivity for TGF‐β and its receptors. Neoplastic cells in CEOTs, AOTs and COCs showed reactivity for HGF, TGF‐β and their receptors. Elevated HGF and TGF‐β reactivity was found in pseudoglandular cells in AOTs, and high expression of their receptors was noted in ghost cells in COCs. Metastasizing ameloblastomas showed similar expression patterns of HGF, TGF‐β and their receptors to those of benign ameloblastomas, while CCOTs and ameloblastic carcinomas had increased HGF expression and low reactivity for TGF‐β and its receptors as compared with benign ameloblastomas.

Conclusions:  Immunohistochemical localization of HGF, TGF‐β and their receptors in tooth germs and epithelial odontogenic tumors supports the hypothesis that HGF and TGF‐β act on epithelial cells via paracrine and autocrine mechanisms. Altered expression of the agents in these epithelial odontogenic tumors, especially subtypes of ameloblastomas, AOTs and COCs, suggests that HGF and TGF‐β signaling might affect differentiation of neoplastic odontogenic epithelial cells. Activated HGF/c‐Met pathway and reduced TGF‐β signaling in CCOTs and ameloblastic carcinomas may be associated with the malignant potential of these epithelial odontogenic tumors.
Atypical lipomatous tumor of the lip with pleomorphic lipoma‐like myxoid area, clinically simulating mucocele
Authors: Hattori Hideo
Published: March 2003

Lipomatous tumor is least common in the oral cavity. We present a case of atypical lipomatous tumor arising in the lower lip of an 81‐year‐old male. Clinical diagnosis was mucocele. The tumor measured 12 mm in diameter with a round shape. It was solid, firm, myxomatous and translucent with a small yellowish focus in the central portion. Histologically, the tumor was a circumscribed and well‐encapsulated mass with prominent myxoid matrix. The central minor portion showed a well‐differentiated liposarcoma. In the myxoid area, lipoblasts and large atypical cells with dense chromatin including floret‐like giant cells were seen in abundance. Atypical lipomatous tumor may be indistinguishable from pleomorphic lipoma and its distinction from the latter is based on location as well as relative abundance of floret‐type giant cells and lipoblasts. According to its abundance in lipoblasts over floret‐like cells, pleomorphic lipoma‐like area in our case could also be a part of atypical lipomatous tumor. It may be possible to interpret myxoid change in our case as to represent a superficial counterpart of myxoid malignant fibrous histiocytoma‐like change reported in the retroperitoneal lesion.
Proliferation and distribution of myoepithelial cells during atrophy of the rat sublingual gland
Authors: Takahashi S. , Shinzato K. , Domon T. , Yamamoto T. , Wakita M.
Published: March 2003

Background:  The present study was aimed to determine the proliferation and distribution of myoepithelial cells during atrophy of rat sublingual glands.

Methods:  The excretory duct of the right sublingual gland of rats was doubly ligated with metal clips to induce atrophy in the gland. The atrophic sublingual glands were taken from 1 to 28 days after duct ligation and examined with single immunohistochemistry for actin as a marker of myoepithelial cells and with immunohistochemical double staining for actin and proliferating cell nuclear antigen (PCNA) as a marker of proliferating cells.

Results:  In unligated sublingual glands, myoepithelial cells embraced acini and intercalated ducts, but not striated and interlobular excretory ducts. In the early stages of atrophy, myoepithelial cells surrounded small ducts but not large ones. However, in the later stages of atrophy, myoepithelial cells were also observed at the periphery of the large ducts. The immunohistochemical double staining showed that there were PCNA‐positive myoepithelial cells in the normal as well as in the atrophic sublingual glands. However, the PCNA labeling indices of myoepithelial cells were low in the unligated and atrophic sublingual glands, and there were no statistically significant differences in these labeling indices.

Conclusion:  The observations suggest that the distribution of myoepithelial cells change during atrophy of rat sublingual glands and that myoepithelial cells have low proliferative activity in both the normal and atrophic condition of rat sublingual glands.
Development of Early Melanocytic Lesions in Transgenic Mice Predisposed to Melanoma
Authors: ZHU HUA , REUHL KENNETH , BOTHA ROSANNE , RYAN KEVIN , WEI JOYCE , CHEN SUZIE
Published: March 2003

We have previously described a line of transgenic mice (TG3) that spontaneously develops heritable malignant melanoma. Histological analysis of these animals during the first postnatal month is described here. In the TG3 line, the number of melanocytes is increased at all anatomical sites to which neural‐crest‐derived melanocytes normally migrate. Clonal expansion and morphological changes of these melanocytes can be detected as early as postnatal day (PND) 15. By PND 30, cells morphologically indistinguishable from the tumor cells of adult transgenic mice were detected in the ear, eye lid and perianal region. These cells are believed to be the precursors of the primary tumors in adult mice. The stepwise development of melanoma in the TG3 line is similar to the stepwise development of melanoma in humans.
Efficient, Long‐term Transgene Expression in Xenopus laevis Dermal Melanophores
Authors: Gatlin Joel , Unett David J. , Lerner Michael R. , Garcia J. Victor
Published: March 2003

Xenopus laevis dermal melanophores provide an excellent model system for the investigation of complex cellular processes. Specifically, the expression of exogenous genes in Xenopus melanophores is the basis of recombinant bioassays for the study of receptor–ligand interactions. However, due to their slow rate of cell division and to the relatively low efficiency of current transfection protocols, long‐term expression of exogenous genes and the generation of stable melanophore cell lines remains problematic. In this report we demonstrate the efficient, long‐term expression of two exogenous proteins, the enhanced green fluorescent protein (EGFP) and the human CD4 (hCD4) cell surface receptor, following stable introduction into Xenopus melanophores via an HIV‐1 based vector. Transduction of melanophores with the EGFP expression vector resulted in up to 80% EGFP+ cells. After 1 year in continuous culture in the absence of antibiotic selection, more than 60% of the cells remained EGFP+. Furthermore, we demonstrate the expression of hCD4 in melanophores for over 9 months in continuous culture in the absence of antibiotic selection. Our results indicate that lentivirus vectors provide an efficient means of introducing genetic information into Xenopus melanophores, resulting in sustained levels of gene expression. The significance of this gene transfer system for the study of cellular signal transduction pathways is discussed.
l‐NAME‐Induced Dispersion of Melanosomes in Melanophores Activates PKC, MEK and ERK1
Authors: Nilsson Harriet M. , Svensson Samuel P.S. , Sundqvist Tommy
Published: March 2003

Melanosome movement represents a good model of cytoskeleton‐mediated transport of organelles in eukaryotic cells. We recently observed that inhibiting nitric oxide synthase (NOS) with Nω‐nitro‐l‐arginine methyl ester (l‐NAME) induced dispersion in melanophores pre‐aggregated with melatonin. Activation of cyclic adenosine 3′,5′‐monophosphate (cAMP)‐dependent protein kinase (PKA) or calcium‐dependent protein kinase (PKC) is known to cause dispersion. Also, PKC and NO have been shown to regulate the mitogen/extracellular signal‐regulated kinase (MEK)‐ERK pathway. Accordingly, our objective was to further characterize the signaling pathway of l‐NAME‐induced dispersion. We found that the dispersion was decreased by staurosporine and PD98059, which respectively inhibit PKC and MEK, but not by the PKA inhibitor H89. Furthermore, Western blotting revealed that ERK1 kinase was phosphorylated in l‐NAME‐dispersed melanophores. l‐NAME also caused dispersion in latrunculin‐B‐treated cells, suggesting that this effect is not due to inhibition of the melatonin signaling pathway. Summarizing, we observed that PKC and MEK inhibitors decreased the l‐NAME‐induced dispersion, which caused phosphorylation of ERK1. Our results also suggest that NO is a negative regulator of phosphorylations that leads to organelle transport.
Analysis of Xanthophore and Pterinosome Biogenesis in Zebrafish Using Methylene Blue and Pteridine Autofluorescence
Authors: Guyader Sylvie Le , Jesuthasan Suresh
Published: March 2003

We have identified two simple methods to analyse xanthophore and pterinosome biogenesis in zebrafish. The first uses methylene blue (methylthionium chloride), a redox dye which specifically labels xanthophores and pterinosomes, while the second uses autofluorescence to detect pteridine levels; these methods may be used to detect the number, location and shape of xanthophores and pterinosomes. These assays were applied to two zebrafish mutants –brie and yobo– and revealed that both mutants have pterinosome biogenesis and pteridine synthesis defects. Additionally, using capillary electrophoresis, we provide evidence that sepiapterin is responsible for the yellow colour and blue‐light induced fluorescence in zebrafish embryos.
Keratinocytes Control the Proliferation and Differentiation of Cultured Epidermal Melanocytes from Ultraviolet Radiation B‐Induced Pigmented Spots in the Dorsal Skin of Hairless Mice
Authors: Hirobe Tomohisa , Furuya Rikako , Akiu Satoru , Ifuku Ohji , Fukuda Minoru
Published: March 2003

Long‐term exposure of ultraviolet radiation B (UVB)‐induced pigmented spots in the dorsal skin of hairless mice of Hos:(HR‐1 X HR//De) F1. Previous study showed that the proliferative and differentiative activities of cultured epidermal melanoblasts//melanocytes from UVB‐induced pigmented spots increased with the development of the pigmented spots. To determine whether the increase in the proliferative and differentiative activities of epidermal melanoblasts//melanocytes was brought about by direct changes in melanocytes, or by indirect changes in surrounding keratinocytes, pure cultured melanoblasts//melanocytes and keratinocytes were prepared and co‐cultured in combination with control and irradiated mice in a serum‐free culture medium. Keratinocytes from irradiated mice stimulated the proliferation and differentiation of both neonatal and adult non‐irradiated melanoblasts//melanocytes more greatly than those from non‐irradiated mice. In contrast, both non‐irradiated and irradiated adultmelanocytes proliferated and differentiated similarly when they were co‐cultured with irradiated adult keratinocytes. These results suggest that the increased proliferative and differentiative activities of mouse epidermal melanocytes from UVB‐induced pigmented spots are regulated by keratinocytes, rather than melanocytes.
Hermansky–Pudlak Syndrome: Vesicle Formation from Yeast to Man
Authors: Huizing Marjan , Boissy Raymond E. , Gahl William A.
Published: March 2003

The disorders known as Hermansky–Pudlak syndrome (HPS) are a group of genetic diseases resulting from abnormal formation of intracellular vesicles. In HPS, dysfunction of melanosomes results in oculocutaneous albinism, and absence of platelet dense bodies causes a bleeding diathesis. In addition, some HPS patients suffer granulomatous colitis or fatal pulmonary fibrosis, perhaps due to mistrafficking of a subset of lysosomes. The impaired function of specific organelles indicates that the causative genes encode proteins operative in the formation of certain vesicles. Four such genes, HPS1, ADTB3A, HPS3, and HPS4, are associated with the four known subtypes of HPS, i.e. HPS‐1, HPS‐2, HPS‐3, and HPS‐4. ADTB3A codes for the β3A subunit of adaptor complex‐3, known to assist in vesicle formation from the trans‐Golgi network or late endosome. However, the functions of the HPS1, HPS3, and HPS4 gene products remain unknown. These three genes arose with the evolution of mammals and have no homologs in yeast, reflecting their specialized function. In contrast, all four known HPS‐causing genes have homologs in mice, a species with 14 different models of HPS, i.e. hypopigmentation and a platelet storage pool deficiency. Pursuit of the mechanism of mammalian vesicle formation and trafficking, impaired in HPS, relies upon investigation of these mouse models as well as studies of protein complexes involved in yeast vacuole formation.
The Pallidin (Pldn) Gene and the Role of SNARE Proteins in Melanosome Biogenesis
Authors: Falcón‐Pérez Juan M. , Dell'angelica Esteban C.
Published: March 2003

This review focuses on the product of the pallidin (Pldn) gene, one of a number of genes that in mice are associated with pigmentation defects and platelet dense granule deficiency. A similar combination of defects is also observed in patients suffering from Hermansky–Pudlak (HPS) and Chediak–Higashi (CHS) syndromes. Pldn encodes a novel, ∼20‐kDa protein that is expressed ubiquitously in mammalian tissues. The pallidin protein was found to bind to syntaxin 13, a member of the syntaxin family of soluble N‐ethylmaleimide‐sensitive factor attachment protein receptors (SNAREs). As SNARE proteins mediate fusion of intracellular membranes, pallidin may play a role in membrane fusion events required for melanosome biogenesis.
Development of an in vitro microassay for glucose quantification in submicrolitre volumes of biological fluid
Authors: Ciantar M. , Spratt D. A. , Newman H. N. , Wilson M.
Published: March 2003

Glucose quantification in serum or plasma is traditionally based on a colourimetric enzymatic assay using commercially available assay kits. Sample volumes of blood or serum are usually in the range of a few microlitres to a few millilitres. However, for biological fluids such as gingival crevicular fluid (GCF), which can only be sampled in submicrolitre volumes, such assays have proven unsuitable. The aim of this study was to develop a reliable and reproducible assay for quantifying glucose in submicrolitre samples of GCF. The assay involved modification of a commercially available kit for glucose quantification. Test solutions of (i) serum and (ii) serum with added glucose at known concentrations (range 50–400 mg/dl) were prepared to simulate GCF and GCF enriched with glucose, respectively. Submicrolitre volumes (range 0.2 µl to 0.8 µl) of the test solutions were added to the reagent solution (200 µl) using a Hamilton syringe. The reaction was performed under standard conditions of time and temperature. The colour change was assayed spectrophotometrically at 492 nm. The results showed that this microassay is sufficiently sensitive to detect 50 mg/dl glucose in 0.2 µl of sample and indicate that the accuracy and sensitivity of this assay make it suitable for glucose quantification in submicrolitre volumes of GCF, particularly relevant to investigations of the relationship between diabetes mellitus and chronic inflammatory periodontal disease. In vivo evaluation of this novel microassay was performed using GCF samples taken from periodontally healthy and chronic periodontitis patients. Using non‐parametric analysis, the results showed that the assay detected statistically significant differences in glucose concentrations between the two patient groups (p < 0.05). Higher glucose levels were detected at the periodontally diseased sites. For each patient, the GCF‐glucose : blood‐glucose ratio was calculated. The results show that this ratio was higher in the periodontitis group (1 : 2) when compared to the healthy group (1 : 9). In conclusion, the results of this investigation have shown that this microassay can quantify glucose in GCF and that GCF‐glucose levels are higher at periodontitis sites.
Morphological evaluation of combined effects of cyclosporin and nifedipine on gingival overgrowth in rats
Authors: Spolidorio L. C. , Spolidorio D. M. , Neves K. A. , Gonzaga H. F. S. , Almeida O. P.
Published: March 2003

It has previously been shown that, while cyclosporin A (CsA) and nifedipine both cause gingival overgrowth in the rat, the combined use of these drugs increases the severity of overgrowth. The aim of this study was to describe the histometry and densities of fibroblasts, collagen fibers and vessels in the gingival tissue of rats that were treated with CsA and nifedipine, either alone or in combination. Rats were treated for 60 days with a daily subcutaneous injection of 10 mg/kg body weight of CsA and/or with 50 mg/kg body weight of nifedipine added to the chow. The results confirmed that CsA causes a more severe overgrowth than nifedipine, and that the combined use of these drugs increases the overgrowth severity. All the rat groups that were studied showed that, as the severity of overgrowth increased, there was a parallel increase in fibroblasts and collagen, and a decrease in vessel content. Therefore, independently of whether the gingival overgrowth was caused by CsA alone, nifedipine alone, or both treatments in combination, the fibroblast and collagen density increased in parallel with the severity of the overgrowth.
Serum IgG antibody response to periodontal pathogens in minority populations: relationship to periodontal disease status and progression
Authors: Craig Ronald G. , Boylan Robert , Yip Julie , Mijares Dindo , Imam Mohammed , Socransky Sigmund S. , Taubman Martin A. , Haffajee Anne D.
Published: March 2003

Differences in periodontal disease prevalence, severity, subgingival microflora and host immune response have been reported for various ethnic/racial groups, which implies that risk factors for destructive periodontal disease progression may also vary in these populations. As it is possible that these differences may be due to confounding variables other than ethnicity/race, we have measured serum IgG antibody response to six periodontal pathogens, and compared these data with microbiological, clinical and demographic parameters in three urban minority populations. The study population consisted of 23 Asiatic, 48 African‐American and 37 Hispanic subjects, who were resident in the greater New York region. Clinical indices that were recorded included pocket depth, attachment level, gingival erythema, bleeding upon probing, suppuration and supragingival plaque. Attachment level measurements were taken twice at each visit, and the difference between the means of pairs of measurements taken at baseline and two months later was used to determine disease progression. Subgingival microbiological species were identified and enumerated using DNA‐DNA checkerboard hybridization. Serum IgG antibody levels to Actinobacillus actinomycetemcomitans serotyopes a and b, Bacteroides forsythus, Campylobacter rectus, Porphyromonas gingivalis and Prevotella intermedia were measured by enzyme‐linked immunosorbant assay (ELISA). Mean serum IgG antibody to P. gingivalis was found to be higher in the African‐American group, while IgG antibody to B. forsythus was lower in the Hispanic group. However, the African‐American group also had greater mean probing depth, attachment loss, number of missing teeth and numbers of individuals within the unskilled occupational group. When the data were analyzed by occupational status, mean serum IgG antibody to P. gingivalis increased from professional to skilled to unskilled groups. For the entire study population, prior disease and subsequent attachment loss were associated with elevated serum IgG antibody to P. gingivalis. Increasing pocket depth, attachment level, gingival erythema and age were also positively correlated with serum IgG antibody to P. gingivalis, but not with serum IgG antibody to the other five subgingival species. No correlation was found between whole‐mouth bacterial levels and homologous serum IgG antibody levels. These results suggest that elevated serum IgG antibody to P. gingivalis reflects destructive periodontal disease status, and may be considered a risk factor for disease progression in these ethnic/racial populations. In addition, although differences in serum IgG antibody profiles to subgingival species were found among the three ethnic/racial groups, environmental and socioeconomic variables may have a greater influence on serum IgG antibody levels in these populations.
Comparison of conventional and TACT® (Tuned Aperture Computed Tomography) digital subtraction radiography in detection of pericrestal bone‐gain
Authors: Chai‐U‐Dom Onanong , Ludlow John B. , Tyndall Donald A. , Webber Richard L.
Published: March 2003

Tuned Aperture Computed Tomography or TACT® is a relatively new technique that transforms correlated two‐dimensional images into a three‐dimensional display. Associating TACT with digital subtraction radiography (TACT‐DSR) may enhance its use in the detection of diseases. This study aims to assess observer performance in the task of detecting simulated bone‐gain in periodontal defects, comparing conventional and TACT DSR. Buccal, lingual and proximal pericrestal bony defects in a human dry skull were imaged with and without increments of crushed‐bone and wax mixtures using standardized vertical bitewing projections, acquired with an intraoral digital receptor in a tomographic X‐ray machine. One hundred and twenty pairs of baseline and follow‐up images were obtained for each imaging modality. Post‐acquisition processing including image‐registration, density‐correction and subtraction operation were applied to both transmission images and TACT‐slices. Eight calibrated observers evaluated the presence or absence of pericrestal bone‐gain using a 5‐point confidence scale. Details about the location of periodontal defects and the amount of bone‐gain for each subtracted image were recorded and used in the statistical analysis. Observer performance and study design factors were analyzed by means of receiver operating characteristic (ROC) curve analysis and ANOVA. Mean values of areas under ROC curves for bone‐gain detection performance were 0.82 for conventional DSR and 0.90 for TACT‐DSR. TACT‐DSR provided statistically superior detection performance of simulated periodontal bone‐gain over conventional DSR for tooth‐obscured defects (p = 0.001) and for the smallest bone mass (p = 0.024). The findings support TACT‐DSR's potential to provide greater sensitivity and technique flexibility in detecting periodontal bone‐gain than standard DSR.
Microbiological, immunological and genetic factors in family members with periodontitis as a manifestation of systemic disease, associated with hematological disorders
Authors: Okada Mitsugi , Awane Saori , Suzuki Junji , Hino Takamune , Takemoto Toshinobu , Kurihara Hidemi , Miura Kazuo
Published: March 2003

The microflora, immunological profiles of host defence functions, and human leukocyte antigen (HLA) findings are reported for a mother, son and daughter who were diagnosed as having ‘periodontitis as a manifestation of systemic diseases, associated with hematological disorders’. Examinations were made of the bacterial flora from the periodontal pocket, neutrophil chemotaxis, neutrophil phagocytosis, and the genotypes (DQB1) and serotypes (DR locus) of HLA class II antigens. Phenotypic analyses of the peripheral lymphocytes were also conducted. The subgingival microflora from the mother was dominated by Gram‐negative rods, especially Porphyromonas endodontalis, Prevotella intermedia/Prevotella nigrescens and Fusobacterium nucleatum. Subgingival microflora samples from the son and daughter were dominated by Gram‐positive cocci and Gram‐positive rods. Through the use of polymerase chain reaction, Campylobacter rectus and Capnocytophaga gingivalis were detected in all subjects, whereas Porphyromonas gingivalis, P. intermedia, and Treponema denticola were not detected in any subjects. All three subjects showed a remarkable level of depressed neutrophil chemotaxis to N‐formyl‐methionyl‐leucyl‐phenylalanine, although their phagocyte function levels were normal, in comparison to healthy control subjects. Each subject had the same genotype, HLA‐DQB1*0601, while the mother had HLA‐DR2 and HLA‐DR8, and the son and daughter had HLA‐DR2 only. In summary, the members of this family showed a similar predisposition to periodontitis with regard to certain host defence functions. It is suggested that the depressed neutrophil chemotaxis that was identified here could be a significant risk factor for periodontitis in this family.
Mechanisms of cytotoxicity of nicotine in human periodontal ligament fibroblast cultures in vitro
Authors: Chang Yu‐Chao , Huang Fu‐Mei , Tai Kuo‐Wei , Yang Li‐Chiu , Chou Ming‐Yung
Published: March 2003

The use of tobacco products significantly contributes to the progression of periodontal disease and poor response to healing following periodontal therapy. The purpose of this study was to determine the effects of nicotine, a major component of cigarette smoking, on human periodontal ligament fibroblast (PDLF) growth, proliferation, and protein synthesis to elucidate its role in periodontal destruction associated with its use. Human PDLFs were derived from three healthy individuals undergoing extraction for orthodontic reasons. At a concentration higher than 2.5 mM, nicotine was found to be cytotoxic to human PDLFs (P < 0.05). Nicotine also significantly inhibited cell proliferation and decreased protein synthesis in a dose‐dependent manner. At concentrations of 50 and 200 µM, nicotine suppressed the growth of PDLFs by 48% and 86% (P < 0.05), respectively. A 10‐mM concentration level of nicotine significantly inhibited the protein synthesis to only 44% of these in the untreated control (P < 0.05). Furthermore, the effects of antioxidants (superoxide dismutase (SOD); catalase and 2‐oxothiazolidine‐4‐carboxylic acid (OTZ) and buthionine sulfoximine (BSO) were added to search for the possible mechanism of action, as well as a method for the prevention, of cigarette smoking‐associated periodontal diseases. The addition of OTZ, a precursor of cysteine that metabolically promotes GSH synthesis, acted as a protective effect on the nicotine‐induced cytotoxicity. However, SOD and catalase did not decrease the nicotine‐induced cytotoxicity. In contrast, the addition of BSO, a cellular GSH synthesis inhibitor, enhanced the nicotine‐induced cytotoxicity. These results indicate that thiol depletion could be the mechanism for nicotine cytotoxicity. The levels of nicotine tested inhibited cell growth, proliferation, and protein synthesis on human PDLFs. This suggests that nicotine itself might augment the destruction of periodontium associated with cigarette smoking. In addition, these inhibitory effects were associated with intracellular thiol levels. Factors that induce glutathione synthesis of human PDLF may be used for further chemoprevention of cigarette smoking‐related periodontal diseases.
Bayesian Pharmacokinetics of Lithium after an Acute Self‐Intoxication and Subsequent Haemodialysis: A Case Report
Authors: Kerbusch Thomas , Math Ron A. A. , Otten Hans M. M. B. , Meesters Eelco W. , Van Kan Hendrikus J. M. , Schellens Jan H. M. , Beijnen Jos H.
Published: March 2003

Abstract: We report a case of a 39‐year‐old male with bipolar affective disorder who was admitted to hospital with an intentional acute lithium intoxication resulting in renal insufficiency. The patient had previously been treated with lithium, risperidone, fluoxetine and lorazepam, and successfully titrated to lithium levels of 0.7 mmol/l. After overdosing, the lithium level was 5.89 mmol/l and haemodialysis was initiated. A full pharmacokinetic time profile of lithium was obtained. After successful haemodialysis treatment, lithium levels recovered below toxic levels of 1.5 mmol/l in 53 hr. Without intervention non‐toxic levels were not expected to have been reached within 6 days, based on computer simulation of predialysis levels. The patient was discharged 6 days after admission without residual symptoms. It was concluded that the lithium intoxication resulted from a combination of lithium overdose and subsequent renal insufficiency due to the overdose. A possible fluoxetine‐risperidone interaction was not considered clinically apparent.
Opposite Effects of Nicotinic Acid and Pyridoxine on Systemic Prostacyclin, Thromboxane and Leukotriene Production in Man
Authors: Saareks Virpi , Ylitalo Pauli , Mucha István , Riutta Asko
Published: March 2003

Abstract: The effects of nicotinic acid (2500 mg orally during 12 hr) and pyridoxine (300 mg orally twice daily for seven days) on the excretion of urinary 2,3‐dinor‐6‐ketoprostaglandin F1α, 11‐dehydrothromboxane B2 and leukotriene E4, the markers of systemic prostacyclin, thromboxane A2 and cysteinyl leukotriene production, respectively, were investigated in healthy male volunteers (n=6–8). Nicotinic acid increased 11‐dehydrothromboxane B2 and leukotriene E4 excretions to 2.6‐ and 2.0 times the initial values (P<0.05), respectively. In the volunteers treated with pyridoxine, 11‐dehydrothromboxane B2 and leukotriene E4 excretions were decreased to 70% (P<0.05) and 65% (P<0.01) of the initial values, respectively, but the excretion of 2,3‐dinor‐6‐ketoprostaglandin F1α was increased 1.7 times (P<0.01). The results suggest that nicotinic acid increases thromboxane and leukotriene synthesis which may not be beneficial for patients with cardiovascular diseases or asthma. In contrast, the increase in prostacyclin production and the inhibition in thromboxane and leukotriene synthesis by pyridoxine might be beneficial in disorders where the production of prostacyclin is decreased and the formation of thromboxane and cysteinyl leukotrienes is enhanced.
Effects on human skin of repetitive ultraviolet‐A1 (UVA1) irradiation and visible light
Authors: Edström Desiree Wiegleb , Porwit Anna , Ros Anne‐Marie
Published: March 2003

Background: Ultraviolet radiation (UVR) has a variety of effects on human skin. Best known are the effects of UVB (290–320 nm) and UVA2 (320–340 nm), which cause DNA damage and increased risk of cancer. However, the effects of UVA1 (340–400 nm) have been not completely investigated.

Methods: The effects of repetitive low doses of UVA1 and visible light were studied in 12 healthy individuals. A part of the buttock was exposed to 20 J/cm2 UVA1 and another part to 126 J/cm2 of visible light three times a week for 4 weeks. Repeated punch biopsies were taken during the 4 weeks of treatment and also 2 weeks after the last irradiation. The avidin‐biotin‐immunoperoxidase technique was used to investigate the expression of p53, p21WAF, bcl‐2, Ki67 and cyclin A.

Results: By comparison to untreated skin, an increased expression of p53 but not p21WAF in keratinocytes was seen. The bcl‐2 protein expression increased slightly after both UVA1 and visible light. An increased staining with Ki67 and cyclin A after UVA1 but not after visible light was observed as a sign of increased proliferation.

Conclusion: These results suggest that suberythemal doses of UVA1 and even visible light may cause DNA damage.
A retrospective review of PUVA therapy at the National Skin Centre of Singapore
Authors: Tran D. , Kwok Y. K. , Goh C. L.
Published: March 2003

Background: Photochemotherapy (PUVA) is beneficial for the treatment of various dermatoses. The introduction of ultraviolet B and narrow‐band ultraviolet B phototherapy has had a significant impact on the role of PUVA in dermatology. This study aims to assess the current role of PUVA in treating dermatoses, in a predominantly Asian population, at the National Skin Centre in Singapore.

Materials and methods:

We reviewed the clinical data of 115 patients who were started on PUVA treatment at the National Skin Centre, Singapore in 1998. We analysed the epidemiology data, the clinical response rate and the adverse effects of PUVA therapy. All of the patients continued to have ongoing maintenance treatment.

Results: Most of our patients were Chinese (74.8%) and male (58.3%), ranging from the ages of 4 to 74 years. Vitiligo (60.9%) was the commonest skin disorder treated with PUVA, followed by psoriasis (20.9%), endogenous eczema (11.3%), mycosis fungoides (3.5%), lichen amyloidosis (2.6%) and prurigo nodularis (0.9%). Most of our patients received paint PUVA (50.4%), 33.9% oral PUVA and 15.7% bath PUVA. The best clinical response – those patients achieving a greater that 50% clearance – was observed in patients with endogenous eczema, psoriasis and mycosis fungoides (76.8%, 73.9% and 60%, respectively). Of the vitiliginous patients, 54.3% experienced a poor response to PUVA therapy. The main side effects were mild erythema and pruritus.

Conclusion: PUVA remains a valuable, well‐tolerated therapeutic option for a variety of dermatoses.
Ultraviolet radiation enhances both the nodular and ulcerative forms of Mycobacterium ulcerans infection in a Crl:IAF(HA)‐hrBR hairless guinea pig model of Buruli ulcer disease
Authors: Cope R. B. , Hartman J. A. , Morrow C. K. , Haschek W. M. , Small P. L. C.
Published: March 2003

Background:
 Ultraviolet radiation (UV) pre‐exposure enhances intracellular mycobacterial infections, however, its effect upon the pathogenesis of the extracellular Mycobacterium ulcerans parasite had not been previously examined. The hypothesis tested was that UV pre‐exposure enhances both the nodular and ulcerative forms of M. ulcerans infection in the Crl:IAF(HA)‐hrBR hairless guinea pig.

Methods:
 Groups of five animals were exposed to total cumulative UV doses of 0 (control), 3 or 30 kJ/m2 followed 3 days later by subcutaneous infection with 3 × 104 CFU of M. ulcerans in order to induce the nodular form of the disease. The resultant nodules were then measured for the next 22 days. The experiment was then repeated using intradermal infection with 2 × 106 CFU in order to induce the ulcerative form of the disease. The resultant ulcers were measured for the next 30 days. In both experiments, the animals were tested for delayed‐type hypersensitivity (DTH) reactivity to Burulin‐S as a marker of the onset of the reactive phase of the disease.

Results:
 Following low inoculum subcutaneous infection, distinct, well‐demarcated, subcutaneously situated skin nodules were present at infected skin sites between 7 and 22 days post‐infection. Between days 14 and 21, the mean nodule diameters of the UV irradiated groups were significantly (P < 0.03) greater than that of the control group. UV pre‐exposure resulted in significant (P < 0.035) suppression of DTH responses to Burulin‐S challenge. High inoculum intradermal infection resulted in the development of ulcerative lesions. Between 10 and 30 days post‐infection, the mean lesion diameters and mean ulcer development times of UV irradiated groups were significantly (P < 0.05) greater than those of the controls. However, UV irradiation did not affect DTH responses to Burulins in the high inoculum experiment. In both experiments, the lesions were histologically consistent with human Buruli ulcer disease. These results demonstrate that UV pre‐exposure results in enhanced M. ulcerans infection in the hairless guinea pig model of Buruli ulcer disease and suggest that UV exposure may be a relevant factor in the pathogenesis of human forms of the disease.
The impact of fetal size and length of gestation on 6‐sulphatoxymelatonin excretion in adult life
Authors: Kennaway D.J. , Flanagan D.E. , Moore V.M. , Cockington R.A. , Robinson J.S. , Phillips D.I.W.
Published: March 2003

Recent studies have shown that intrauterine growth retardation or fetal distress in human infants is associated with a pronounced reduction in melatonin secretion during the first 3 months of life. It is not known whether these associations persist beyond infancy. We have therefore examined the relationship between birthsize and melatonin secretion in 159 men and women aged 20, born in Adelaide, South Australia. Melatonin secretion was estimated by analysing the overnight urinary excretion of 6‐sulphatoxymelatonin. The overnight excretion ranged from 1.7 to 128.9 nmoles/subject, was higher in women than in men (46.5 vs 34.1 nmoles, P=0.003) and was significantly negatively correlated with the body mass index (P=0.006). Excretion correlated with both birthweight and ponderal index at birth (P=0.04 and P=0.01 respectively after adjustment for gestational age) and also fell with increased duration of gestation (P=0.007). The effects of adult body mass index added to that of low birthweight in predicting 6‐sulphatoxymelatonin excretion. These data suggest that urinary 6‐sulphatoxymelatonin excretion was impaired in adults who were growth restricted prenatally or were delivered after 40 weeks gestation.
Melatonin induces alterations in protein expression in the Xenopus laevis retina
Authors: Wiechmann Allan F. , Komori Naoka , Matsumoto Hiroyuki
Published: March 2003

The hormone melatonin is synthesized by pinealocytes and retinal photoreceptors with a diurnal rhythm. Melatonin produced in the retina at night is thought to exert local modulatory effects by binding to specific receptors in several different retinal cell types. The mechanisms by which melatonin influences circadian activity in retinal cells is poorly understood. Suppression of cyclic AMP synthesis appears to be a major signaling pathway in response to melatonin receptor binding in many tissues. A potential downstream consequence of melatonin‐induced changes in cyclic AMP concentrations and protein phosphorylation is the up‐ or down‐regulation of expression of specific genes. In this report, we examined the changes in expression levels of specific proteins in the neural retina and retinal pigment epithelium (RPE) in response to melatonin treatment, because both of these tissues express melatonin receptors. Neural retina and RPE isolated from the eyes of Xenopus laevis were treated with or without 1 μM melatonin for 6 hr, then the rapidly synthesized tissue proteins were radiolabeled by a 15 min incubation with 35S‐methionine, and the proteins were subsequently analyzed by two‐dimensional gel electrophoresis and autoradiography. In both the neural retina and RPE, the densities of some specific proteins were altered in response to melatonin treatment, and the few protein spots that were altered were distinct between the two tissues. These results support the concept that one function of melatonin may be to regulate the expression of specific genes and the consequent protein levels, and that the target genes may differ according to the cell or tissue type.
Effects of subchronic and chronic melatonin treatment on somatostatin binding and its effects on adenylyl cyclase activity in the rat frontoparietal cortex
Authors: Izquierdo‐Claros Rosa María , Boyano‐Adánez María del Carmen , Arilla‐Ferreiro Eduardo
Published: March 2003

Abstract: Melatonin and somatostatin are known to exert similar effects on locomotor activity. We have previously demonstrated that acute melatonin treatment regulates somatostatin receptor function in the rat frontoparietal cortex. However, the effects of subchronic and chronic melatonin treatment on the somatostatin receptor‐G protein–adenylyl cyclase system in the rat frontoparietal cortex are unknown. Melatonin was administered subcutaneously at a daily dose of 25 μg/kg for 4 days, 1 wk or 2 wk. Twenty‐four hours after the last injection, the animals were sacrificed. Melatonin did not alter the somatostatin‐like immunoreactivity content in the frontoparietal cortex from control and melatonin‐treated rats during any of the previously indicated periods. Four days of melatonin administration induced both an increase in the number of [125I]‐Tyr11‐somatostatin receptors and a decrease in the affinity of somatostatin for its receptors in frontoparietal cortical membranes. The increased number of somatostatin receptors in the melatonin‐treated rats was associated with an increased capacity of somatostatin to inhibit basal and forskolin‐stimulated adenylyl cyclase activity. Melatonin administration for 4 days induced a higher adenylyl cyclase activity both under basal conditions and after direct stimulation of the enzyme with forskolin. No significant differences were observed in the function of Gi proteins in the 4‐day melatonin‐treated rats. Western blot analyses showed that the 4‐day melatonin treatment reduced Giα2 levels, without altering the amount of Giα1. These melatonin‐induced changes reverted to control values after 7 or 14 days of treatment. Altogether, the present findings suggest that subchronic melatonin treatment modulates the somatostatin receptor/effector system in the rat frontoparietal cortex.
Some biochemical properties of melatonin and the characterization of a relevant metabolite arising from its interaction with H2O2
Authors: Carampin Paolo , Rosan Stefania , Dalzoppo Daniele , Zagotto Giuseppe , Zatta Paolo
Published: March 2003

Abstract: Melatonin is an efficient protector against hydrogen peroxide(H2O2)‐induced lipid peroxidation and acts in a concentration‐dependent manner. Hydrogen peroxide is rather a water stable molecule which is able to cross the cell membrane much better than some important free radicals such as superoxide anion, and consequently its local production can lead to significant spread by diffusion. In this paper we report data regarding some biochemical properties of melatonin as well as the chemical characterization of the major product formed from the interaction between melatonin and H2O2 (N1‐acetyl‐N2‐formyl‐5‐methoxykynuramine) that are consistent with previous data reported by other authors. The effect of melatonin on catalase, glutathione peroxidase and superoxide dismutase in in vitro and in vivo experiments is also reported.