bluuebunny/crossref_metadata_2025 huggingface dataset:
Apoptotic pathways in primary biliary cirrhosis and autoimmune hepatitis
Authors: Fox Christine K. , Furtwaengler Alex , Nepomuceno Ronald R. , Martinez Olivia M. , Krams Sheri M.
Published: March 2003

Abstract: Background/Aims: Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are two autoimmune diseases with unknown etiologies that primarily target the liver. In both diseases, liver lesions are accompanied by large infiltrates of mononuclear cells. The purpose of this study was to determine if either the Fas‐mediated or the granule‐exocytosis pathways contribute to apoptosis in these diseases. Methods: To determine the involvement of apoptosis in tissue injury we examined liver tissue for DNA fragmentation and morphological characteristics of apoptosis. The major cytotoxic pathways of activated lymphocytes were compared by quantitating the levels of transcripts for FasL and granzyme B, and expression was confirmed by immunoprecipitation of these molecules. Results: In both diseases, apoptosis was observed. However, the main cell types undergoing apoptosis were hepatocytes in AIH, and biliary epithelial cells in PBC. In AIH the levels of FasL and granzyme B mRNA were increased over the levels detected in normal liver, while in PBC only the levels of granzyme B were elevated. Additionally, in AIH, the ratio of FasL transcripts to granzyme B transcripts was elevated, reflecting a possible increase in the relative contribution of FasL to the progression of the disease. Immunoprecipitation studies further support an increase in FasL protein expression in AIH. Conclusions: These data suggest that both FasL and granzyme B contribute to the apoptosis observed in AIH and PBC. However, FasL appears to play a more prominent role in the induction of hepatocyte apoptosis and tissue destruction in AIH.
Histological patterns of rejection using oral microemulsified cyclosporine and tacrolimus (FK506) as monotherapy induction after orthotopic liver transplantation
Authors: Chau Tai Nin , Quaglia Alberto , Rolles Keith , Burroughs Andrew Kenneth , Dhillon Amar Paul
Published: March 2003

Abstract: Background/Aims: We describe the histological patterns of rejection in liver transplant recipients using induction therapies with cyclosporine and tacrolimus monotherapy compared with standard triple therapy as historical control. Methods: Patients formed part of the initial cohort in an open‐labelled, randomised pilot study and were selected consecutively if they had histological rejection and no other confounding diagnoses. There were 13 patients in the cyclosporine monotherapy group (CsA), 11 in the tacrolimus monotherapy group and 13 in the triple therapy group (CAP). The histology of liver biopsies was reassessed blindly and the severity of rejection was recorded. Results: The total Royal Free Hospital (RFH) rejection scores as well as other histological features (zone 3 haemorrhage, apoptosis in zones 1 and 3, steatosis, cholestasis, nuclear vacuolation, lymphoblasts and ballooning) were comparable in the three groups. There was no difference in individual components of the histological features comprising the diagnosis of rejection, except that the portal inflammation score was significantly lower in the tacrolimus group when compared with the CsA group (p=0.04). There was no significant difference in the number of patients with moderate/severe rejection between the three groups. Overall, there was no significant increase in histological severity of rejection in the monotherapy groups.

Conclusions: The results suggest that the monotherapy may be as effective as the triple therapy in the initial post‐transplant phase and that no particular graft histological changes were associated with the type of treatment.
Correlation of clinical characteristics with detection of hepatitis B virus X gene in liver tissue in HBsAg‐negative, and HCV‐negative hepatocellular carcinoma patients
Authors: Higashi Yoichiro , Tada Shuji , Miyase Shuichi , Hirota Kazuhiko , Imamura Haruo , Kamio Takihiro , Suko Hironobu
Published: March 2003

Abstract: Purpose: We studied the clinical features and the etiology of hepatitis B virus surface antigen (HBsAg)‐negative and antibody to hepatitis C virus (anti‐HCV) negative patients with hepatocellular carcinoma. Methods: A total of 550 patients, hospitalized with an initial diagnosis of HCC were retrospectively studied. Eighty‐one of these patients were HBsAg‐positive (HB group), 404 patients were anti‐HCV positive (HC group). The other 65 patients were negative for both HBsAg and for anti‐HCV (NBNC group). We purified HBV‐X gene from HCC or non‐tumorous liver tissue of 23 NBNC patients using PCR. Results: Clinical features of NBNC as compared with HB and HC patients were as follows, respectively: non‐cirrhosis rate (%): 57,37,15 (P = 0.02 for HB, P < 0.00001 for HC), the proportion of patients with normal ALT concentrations (%): 59,28,10 (P = 0.0002 for HB, P < 0.00001 for HC). Forty of 59 NBNC patients (68%) had anti‐HBs and/or anti‐HBc (healthy controls: 29%, P < 0.00001) and two of 56 had serum HBV DNA. Twelve of 23 NBNC patients had HBV‐X gene in HCC and/or non‐cancerous liver tissues (52%). None of 52 had serum HCV RNA. Conclusions: The NBNC patients with HCC had a higher frequency of non‐cirrhotic liver without liver injury. The presence of the HBV‐X gene in HCC suggests a possible role of past HBV infection in the development of HCC. About half of NBNC HCC is associated with seronegativity for HBsAg and positivity for the HBV‐X gene in liver tissue.
Recombinant human gonadotropins for macaque superovulation: Repeated stimulations and post‐treatment pregnancies
Authors: VandeVoort C.A. , Tarantal A.F.
Published: March 2003

This report summarizes data from the superovulation and ultrasound‐guided follicular aspiration of 40 female rhesus monkeys (Macaca mulatta) with recombinant human gonadotropins. Of the animals treated, 12 were stimulated for only one cycle, either because of a poor response to the hormones or due to ectopic ovarian position precluding ease of access via ultrasound. The majority of animals were stimulated for a minimum of 3 cycles and 3 females continued to respond for a minimum of 8 and a maximum of 10 cycles. For those animals with repeated stimulation cycles, the number of follicles developed during each of the stimulation protocols remained relatively comparable. Of the animals mated since cessation of treatment, 70% conceived. There was no difference between the conception rate in this subset of animals and the rest of the macaque breeding colony. These data indicate that participation in these studies does not impact on the reproductive potential of female rhesus monkeys.
Three spontaneous lymphomas in a colony of cotton‐top tamarins (Saguinus oedipus)
Authors: Hofmann Petra , Kahnt Konstanze , Mätz‐Rensing Kerstin , Brack Manfred , Kaup Franz‐Josef
Published: March 2003

Cotton‐top tamarins are well known for their prevalence to idiopathic colitis and adenocarcinomas. At the same time, information on the incidence of spontaneous lymphomas in this highly endangered species is rare. Records, 212 in total, of cotton‐top tamarins (Saguinus oedipus) necropsied at the German Primate Centre between 1979 and 1998 were viewed to establish the prevalence of lymphoid neoplasms. Neoplastic lymphoid cell growth was mentioned in three necropsy records. Immunohistology was performed in all three cases on the remaining formalin‐fixed, paraffin‐embedded tissue using antibodies against CD20, CD3, lysozyme, Ki‐67, IgM, IgG, kappa, lambda and EBNA‐2. Combining histological and immunohistological results, the lymphomas could be differentiated into two low‐grade T‐cell lymphomas and one high‐grade multicentric polymorphic B‐cell lymphoma. This corresponds to a 1.4% incidence of lymphomas in our cotton‐top tamarin population over a period of 19 years. Although frozen material was not available and virological testing could not be carried out, clinical or histological evidence did not support an aetiological role of Herpes (H.) saimiri, H. ateles, simian T‐cell leukaemia virus type 1 (STLV‐1) or Epstein–Barr‐related herpesvirus in any of these cases. The lymphomas were considered to be spontaneous.
Evaluation of low‐grade iron carbide as a reagent for enhanced nitrogen desorption in steel melts
Authors: Lee M. S. , Trimble D. J. , Wibberley L. J.
Published: March 2003

This paper gives an overview of the theoretical and practical issues involved in nitrogen control in steelmaking. A series of bench‐scale experiments have been carried out to assess the ability of low‐grade iron carbide to enhance nitrogen desorption from liquid steel. It is speculated that fine iron carbide will enhance nitrogen desorption by generating fine CO bubbles in liquid steel. The findings of this study are particularly applicable to the development of low nitrogen practices for the EAF.
Hot ductility behavior and HAZ hot cracking susceptibility of 7475‐T7351 aluminum alloy
Authors: Yang Ji‐Gang , Ou Bin‐Lung
Published: March 2003

The elevated temperature mechanical properties and hot crack susceptibility of the aluminum alloys, 7475‐T7351 and 7005‐T1 were evaluated using a Gleeble hot‐ductility test. The 7475 alloy exhibited lower hot ductility and strength, significantly poorer ductility recovery on cooling from the nil‐strength temperature, considerably wider brittle temperature range (BTR) and crack susceptible region (CSR), and thus greater susceptibility to heat‐affected zone (HAZ) hot cracking, as compared to the 7005 alloy. Longitudinal samples of 7475 had a lower crack susceptibility than short‐transverse 7475 samples. The results showed good agreement with those of the spot‐Varestraint tests. Scanning electron microscopy (SEM) revealed that the ductility loss was accompanied by fracture transition from ductile transgranular mode to brittle intergranular mode. The HAZ hot cracking in alloy 7475 due to the loss of ductility was primarily caused by liquation of low‐melting‐point grain boundary segregates or eutectics that contained high amounts of Mg, Cu, and Zn.
The assessment of thermodynamic parameters in the Al2O3‐Y2O3 system and phase relations in the Y‐Al‐O system
Authors: Fabrichnaya Olga , Seifert Hans Jürgen , Ludwig Thomas , Aldinger Fritz , Navrotsky Alexandra
Published: March 2003

Thermodynamic parameters for solid and liquid phases in the Al2O3‐Y2O3 system are assessed using new calorimetric measurement for the YAG (Y3Al5O12), YAP (YAlO3) and YAM (Y4Al2O9) phases. The calculated phase diagram of the Al2O3‐Y2O3 system is in reasonable agreement with experimental data. According to the calculations, the YAP phase melts congruently and is stable down to the low temperatures, while the YAM phase disproportionates to a mixture of YAP and Y2O3 phases at temperatures below 1385 K. The calculated entropy of the YAG phase 300.1 J/(mol · K) is between 2 experimentally determined values 284.8 and 349.1 J/(mol · K). However, the difference between calculated and experimental values exceeds uncertainty limits of adiabatic calorimetry data. The enthalpies of melting for the YAG and YAP phases calculated in this study are in reasonable agreement with DTA measurements. The calculated enthalpy of melting for the YAG phase is not consistent with estimates based on solution calorimetric data. New independent measurement of the standard entropy and enthalpy of melting are desirable for the YAG, YAM and YAP phases. The liquidus surface and isothermal section at 2000 K for ternary Al‐Y‐O system are calculated in this study.
Supercooled liquid properties versus glass formation:application to Al‐rich alloys
Authors: Clavaguera Narcís , Clavaguera‐Mora Maria Teresa
Published: March 2003

Glass formation when quenching from the liquid state is discussed in terms of the thermodynamics and kinetics of the stable/metastable competing phases. Recent developments have shown exceptionally good glass‐forming ability in a number of multicomponent systems which exhibit a wide supercooled liquid region before crystallisation, low critical cooling rate, (between 1 and 500 K · s−1) and, consequently, large critical sample thickness (up to 40 mm). Thermodynamics is required to relate the glass transition temperature, Tg, to the energetics of the supercooled liquid. Kinetic destabilisation of equilibrium solidification and, consequently, glass‐forming ability are favoured by the high‐viscosity values achieved under continuous cooling. The relative thermal stability of the supercooled liquid depends on the thermodynamic driving force and interfacial energy between each competing nucleating phase and the molten alloy. Following a procedure already established for binary systems, the thermodynamic optimisation of the Al‐rich part of the Al‐Ni‐Nd‐Cu system by the Calphad method is applied to the kinetics of the nanocrystallisation of the FCC‐(Al) for the Al87Ni7Nd3Cu3 alloy. The Al‐rich corner of the quaternary system is evaluated using the CALPHAD method. The thermodynamical data set obtained is used to calculate the thermodynamic functions needed to model nucleation and crystal growth from the undercooled liquid alloy. The glass formation is discussed in terms of the kinetics of the processes.
Modelling viscosity of alumina‐containing silicate melts
Authors: Zhang Ling , Jahanshahi Sharif
Published: March 2003

A structurally‐related model for the viscosity of silicate melts developed by the present authors has been extended to melts containing alumina. In the binary Al2O3‐SiO2 system, viscosity was modelled by treating Al2O3 as a metal oxide, i.e., as a network modifier based on the similarities in the general behaviour of the binary systems. The ternary and higher‐order systems were modelled using only the parameters for binary silicate melts without introduction of high‐order parameters. The model has been validated for ternary and higher‐order (up to 6‐component) aluminosilicate melts over broad temperature and composition ranges against an extensive collection of experimental data. Good agreement between the experimental data and the viscosity values calculated by the model was obtained.
The distribution of cobalt between Co‐Cu alloys and Al2O3‐FeO‐Fe2O3‐SiO2 slags
Authors: Derin Bora , Yücel Onuralp
Published: March 2003

The solubility of cobalt in alumina‐containing iron silicate slags (0.092–3.365 wt % Co) in equilibrium with cobalt‐copper‐iron alloys (0.070–6.351 wt% cobalt) and oxygen pressures of 1.125 · 10−8, 2.396 · 10−9 and 4.536 · 10−10 atm has been studied at 1673 K. It has been found that: (i) the solubility of cobalt in the slag increased with increase in concentration of cobalt in the alloy, and also increased with increasing oxygen partial pressure in the atmosphere at a fixed concentration of cobalt in alloy; and (ii) the activity coefficient of cobalt oxide in the slag increased with increasing cobalt oxide in the slag and/or decreasing oxygen partial pressure in the system.
Moulding properties of synthetic sand mixtures. A comparative study
Authors: Orumwense F. F. O.
Published: March 2003

A comparative study has been carried out on the foundry qualities of synthetic moulding sand mixtures prepared from indigenous sand and clays of different plasticity (Enugu sand, Enugu fireclay and Ukpor clay). The effect of clay and water content on compressive strength and gas permeability in the green state was investigated. Results show that the more plastic Ukpor clay is a better binder and that moulding sand with up to 8 wt% fireclay, 3 wt% water; and 10 wt% Ukpor clay, 4 wt% water ensure a good combination of all working properties investigated. In the dry state the compressive and tensile strengths of the moulding sand showed a steady increase with increased clay content. With the addition of sawdust and coal dust, the latter showed best improvement on both the dry compressive and tensile strengths. Excellent collapsibility and high friability (12.53% for Ukpor clay‐bonded mixture and 10.35% for fireclay‐bonded mixture) were exhibited, but the friability values were reduced to about 1% by adding up to 3 wt% H2O for Ukpor clay‐bonded mixtures. The negative effect on the collapsibility was partially eliminated by the addition of 3 wt% sawdust. The study also shows that synthetic sand would be suitable for steel and general‐purpose casting, considering the low binder contents of the mixtures.
Analytical model of pass‐by‐pass strain in bar rolling and its verification
Authors: Lee Youngseog , Kim Byung‐Min
Published: March 2003

This paper presents an analytical model for predicting the pass‐by‐pass strain, defined as maximum averaged effective (equivalent) plastic strain at a given pass, in a bar (or rod) rolling process. The model has been based on the equivalent rectangle approximation method which makes the curved configuration of the deformed section into a simplified rectilinear configuration and the hypothesis of parallelepiped deformation of material. Experimental and numerical studies were carried out to investigate the validity of the analytical model. For experimental verification, plate rolling and bar rolling experiments were designed that consisted of a four‐pass oval‐round (or round‐oval) rolling sequence such that during rolling the material experiences the same amount of the strain at each pass. The microstructures and mechanical behaviors of specimens acquired from the two types of experiment were compared. A commercial finite element analysis program, DEFORM, was also used to examine the validity of the analytical model numerically. A similarity between the mechanical behaviors of the plate‐rolled and bar‐rolled specimens was found at each pass. It was also seen that the strains calculated by the analytical model were in agreement with the averaged effective plastic strain computed by finite element simulation.
Effect of surface‐active species on the foam stability in the EAF slag system
Authors: Yi Sang‐Ho , Kim Sung‐Man
Published: March 2003

To determine the proper slag chemistry for sound slag foaming characteristics, the concept of a gas hold‐up index (εG) was introduced using a special device during an EAF operation. The gas hold‐up index became larger with smaller bubble sizes in the final foaming slag, indicating there was a strong relationship between foam stability and bubble size. Proper slag basicity was determined by measuring gas hold‐up indices and effects of the slag components were also defined by the index. Trends of foam stability as a function of basicity and possible surface‐active elements were considered to evaluate the foam stability. Gas bubble sizes associated with the foam stability were also dealt with by measuring final foamy slags.
Utilization of ferrous leach liquor to synthesize gamma ferric oxide
Authors: Narasimhan B. R. V. , Prabhakar S. , Rao K. Hanumantha , Manohar P. , Gnanam F. D.
Published: March 2003

The production of pigment grade titanium dioxide involves leaching of ilmenite with acids that also results in the formation of ferrous sulfate/chloride. Usually the ferrous salts are spray‐roasted to regenerate the sulfuric acid/hydrochloric acid for recycling. However, the quantities of ferrous leach liquor and the capital cost of the regeneration plant dictate the viability of regeneration of acids. In the case of smaller ilmenite processing plants, the regeneration of the acid is not economical and warrants alternate methods of using the ferrous leach liquor. The present paper describes a novel method of synthesizing gamma ferric oxide from ferrous leach liquor obtained from a titanium dioxide pigment plant situated in south India. The partial precipitation technique is employed to purify the ferrous leach liquor and make it suitable for the synthesis. Sodium carbonate is used to precipitate iron as ferrous carbonate and is directly calcined to yield gamma ferric oxide. Experiments were conducted to study the effect of heating rate, condition of the precipitate, whether dry or wet, and extent of oxidation of ferrous on the magnetic properties such as coercivity and specific magnetization. Cobalt‐doped gamma ferric oxide was also prepared by the carbonate precipitation route.
Integrating optimal foraging and optimal oviposition theory in plant–insect research
Authors: Scheirs Jan , De Bruyn Luc
Published: March 2003

The current approach for studying host selection by phytophagous insects is mainly based on optimal oviposition theory, i.e. the preference–performance hypothesis. Almost no attention has been given to optimal foraging theory. However, recent papers and additional evidence given in this work illustrate that also optimal foraging may shape host preference patterns of phytophagous insects. Therefore and because optimal foraging and optimal oviposition may oppose conflicting needs to phytophagous insects, we plea for an integration of optimal foraging and optimal oviposition in plant–insect research. We argue how this may improve our understanding of plant–insect interactions.
Infection by the systemic fungus Epichloë glyceriae and clonal growth of its host grass Glyceria striata
Authors: Pan Jean J. , Clay Keith
Published: March 2003

Many plant species have the ability to expand laterally through space by clonal growth. Plant pathogens can affect clonal growth characteristics thereby altering the success of host plants within populations and of clonal species within communities. We conducted a greenhouse experiment to determine the effects of the systemic fungal pathogen, Epichloë glyceriae, on clonal growth patterns of its host grass, Glyceria striata. We found that infected and uninfected plants produced similar total biomass and numbers of tillers plus primary stolons per mother ramet. However, biomass allocation to tillering (vegetative growth) vs stolon production (clonal growth) was significantly affected by pathogen infection. Infected plants produced more stolons and clonal growth biomass than uninfected plants while mother ramets of uninfected plants produced more tillers and biomass than infected plants. Stolon architecture of infected and uninfected plants also differed. In two of three populations, infected plants produced stolons with greater biomass and shorter spacer lengths, even though mean stolon lengths were similar for infected and uninfected plants. These results contrast strongly with most other clonal plant‐pathogen systems where infected plants are less vigorous and have reduced clonal growth compared to uninfected plants. Greater clonal growth may be an effective mechanism for host genotypes to persist and spread when seed production is prevented, as is the case with castrating pathogens like Epichloë glyceriae.
The effects of habitat manipulation on population distribution and foraging behavior in meadow voles
Authors: Pusenius Jyrki , Schmidt Kenneth A.
Published: March 2003

Individuals, free to choose between different habitat patches, should settle among them such that fitness is equalized. Alternatives to this ideal free distribution result into fitness differences among the patches. The concordance between fitnesses and foraging costs among inhabitants of different quality patches, demonstrated in recent studies, suggests that the mode of habitat selection and the resulting fitness patterns may have important implications to the resource use of a forager and to the survival of its prey. We studied how coarse scale selection between habitat patches of different quality and quitting harvest rate in these patches are related to each other and to fine scale patch use in meadow voles (Microtus pennsylvanicus). To demonstrate these relationships, we manipulated habitat patches within large field enclosures by mowing vegetative cover and adding supplemental food according to a 2×2 factorial design. We tracked vole population densities, collected giving‐up densities (GUDs, a measure of patch quitting harvest rate), and monitored the removal of seeds from lattice grids with 1.5 m intervals (an index of fine‐scale space use) in the manipulated habitat patches. Changes in habitat quality induced changes in habitat use at different spatial scales. In preferred habitats with intact cover, voles were despotic and GUDs were low, but increased with the addition of food. In contrast, voles in less‐preferred mowed habitats settled into an ideal free distribution, GUDs were high and uninfluenced by the addition of food. Seed removal was enhanced by the presence of cover but inhibited by supplemental food. Across all treatments, vole densities and GUDs were strongly correlated making it impossible to separate their effects on seed removal rates. However, this relationship broke down in unmowed habitats, where GUDs rather than vole density primarily influenced seed removal by voles. GUDs and seed removal correlated with predation on tree seedlings formerly planted into the enclosures, demonstrating the mechanisms between coarse‐scale habitat manipulations and community level consequences on a forager's prey.
The costs of immunological challenge to developing mountain chickadees,Poecile gambeli,in the wild
Authors: Whitaker Shayna , Fair Jeanne
Published: March 2003

The tradeoff between immunocompetence and development in avian species could have long‐term consequences relating to fitness. This study investigated the developmental cost of mounting a humoral immune response in growing mountain chickadees,Poecile gambeli. We immunologically challenged nestling chickadees using nonpathogenic antigens of either Newcastle disease virus vaccine or sheep red blood cells. Body mass, tarsal length, haematocrit, total plasma protein, and survival did not vary significantly between antigen treatment groups and control groups. Developmental stability was assessed using fluctuating asymmetry (FA) between the right and left ninth primary feather length. FA was increased significantly in the antigen‐challenged birds. This result indicates that the up‐regulation of the humoral immune response was developmentally costly to the nestlings by causing an increase in FA.
Alterations of p16/MTS1 gene in oral squamous cell carcinomas from Taiwanese
Authors: Lin Shu‐Chun , Chang Kuo‐Wei , Chang Che‐Shoa , Liu Tsung‐Yun , Tzeng Yueng‐Sheng , Yang Feng‐Shuo , Wong Yong‐Kie
Published: March 2003

Abstract: To determine the alterations of the p16/MTS1 gene in oral squamous cell carcinoma (OSCC), we examined in Taiwanese patients the mutation, deletion and methylation of p16/MTS1 in primary OSCCs associated mostly with betel quid (BQ)/tobacco use. Among 110 tumors undergoing mutational analyses, seven (6%) showed mutations in exon 2 or the intron 1/exon 2 splice site. All but one mutation disrupted the encoded proteins. Base transitions represented the vast majority (6/7) of the mutations identified in BQ/tobacco consuming subjects. It was noted that 15/56 (27%) tumors examined by restriction fragment methylation analysis revealed a significant level of methylation in different loci of exon 1 as compared with the respective non‐cancerous tissue. Mutation of p16/MTS1 was exclusively identified in carcinomas of buccal mucosa, whereas methylation of the p16/MTS1 promoter region occurred preferentially in carcinomas of the tongue (54%) rather than at other sites (22%). Homozygous deletion was not found in 56 paired samples examined, nor was hemizygous deletion indicated in 12 informative cases. The results indicated aberrant methylation and mutation as the molecular abnormality of p16/MTS1 in the OSCC from Taiwanese.
Synergistic effects of nicotine on arecoline‐induced cytotoxicity in human buccal mucosal fibroblasts
Authors: Chang Yu‐Chao , Hu Chao‐Chin , Tseng Tsui‐Hwa , Tai Kuo‐Wei , Lii Chong‐Kuei , Chou Ming‐Yung
Published: March 2003

Abstract: Areca quid chewing has been linked to oral submucous fibrosis and oral cancer. Arecoline, a major areca nut alkaloid, is considered to be the most important etiologic factor in the areca nut. In order to elucidate the pathobiological effects of arecoline, cytotoxicity assays, cellular glutathione S‐transferase (GST) activity and lipid peroxidation assay were employed to investigate cultured human buccal mucosal fibroblasts. To date, there is a large proportion of areca quid chewers who are also smokers. Furthermore, nicotine, the major product of cigarette smoking, was added to test how it modulated the cytotoxicity of arecoline. At a concentration higher than 50 μg/ml, arecoline was shown to be cytotoxic to human buccal fibroblasts in a dose‐dependent manner by the alamar blue dye colorimetric assay (P<0.05). In addition, arecoline significantly decreased GST activity in a dose‐dependent manner (P<0.05). At concentrations of 100 μg/ml and 400 μg/ml, arecoline reduced GST activity about 21% and 46%, respectively, during a 24 h incubation period. However, arecoline at any test dose did not increase lipid peroxidation in the present human buccal fibroblast test system. The addition of extracellular nicotine acted synergistically on the arecoline‐induced cytotoxicity. Arecoline at a concentration of 50 μg/ml caused about 30% of cell death over the 24 h incubation period. However, 2.5 mM nicotine enhanced the cytotoxic response and caused about 50% of cell death on 50 μg/ml arecoline‐induced cytotoxicity. Taken together, arecoline may render human buccal mucosal fibroblasts more vulnerable to other reactive agents in cigarettes via GST reduction. The compounds of tobacco products may act synergistically in the pathogenesis of oral mucosal lesions in areca quid chewers. The data presented here may partly explain why patients who combined the habits of areca quid chewing and cigarette smoking are at greater risk of contracting oral cancer.
Type II nitric oxide synthase (NOS2) expression correlates with lymph node status in oral squamous cell carcinoma
Authors: Brennan Peter A. , Palacios‐Callender Miriam , Zaki Graeme A. , Spedding Anne V. , Langdon John D.
Published: March 2003

Abstract: In tumour biology, nitric oxide (NO) has a complex array of concentration‐dependent actions, including both inhibitory and promoting effects. It is thought that the levels of NO found in many human cancers lead to enhanced angiogenesis and tumour dissemination. In the current study, we assessed the immunohistochemical expression of the enzyme type II nitric oxide synthase (NOS2) in 41 cases of oral squamous cell carcinoma and correlated the findings with lymph node status. A significant relationship was found between NOS2 expression and lymph node metastasis (P<0.0002). Furthermore, lymph node metastasis correlated with the degree and intensity of staining seen (P<0.001). No correlation was found between the size of the primary tumour, degree of tumour differentiation or smoking status and NOS2 staining. Western blotting confirmed NOS2 protein expression in select cases. As with many other human tumours, NOS2 is not a ubiquitous finding in oral cancer. Its expression may be of value in assessing lymph node status prior to surgery, and it represents a target for possible therapeutic manipulation.
Expression profile of human defensins and antimicrobial proteins in oral tissues
Authors: Dunsche Anton , Açil Yahya , Siebert Reiner , Harder Jürgen , Schröder Jens‐M. , Jepsen Søren
Published: March 2003

Abstract: Antimicrobial peptides and proteins are an important part of the innate host defense. In the present study, the expression profile of three human alpha‐defensins, of two human beta‐defensins (hBD) and of phospholipase A‐2 (PLA‐2) and lysozyme was determined by reverse transcription‐polymerase chain reaction (RT‐PCR) in 56 non‐inflamed and 18 inflamed oral tissue samples and primary oral keratinocytes and fibroblasts. The transcripts for hBD‐1 and ‐2 as well as for PLA‐2 and lysozyme were found to be widely expressed. In the group of the alpha‐defensins, the message for the human neutrophil peptide‐1 (HNP‐1) was frequently detected, whereas an expression of human Paneth’s cell defensin‐5 (HD‐5) was identified in only a minority of samples. Transcripts for HD‐6 were not detectable in any sample. Oral keratinocytes but not fibroblasts contained transcripts for the beta‐defensins, suggesting that these defensins are produced in the epithelial compartment. In contrast, mRNA expression of neutrophil‐derived HNP‐1 and PLA‐2 was not observed in any of these cells. These results suggest an important role for hBD‐1 and hBD‐2 in the innate oral epithelial host defense.
Diffusion of reduced arecoline and arecaidine through human vaginal and buccal mucosa
Authors: Van der Bijl P. , Van Eyk A. D. , Van Wyk C. W. , Stander I. A.
Published: March 2003

Abstract: Because alkaloids from areca nut, arecoline and arecaidine, have been implicated in the development of oral submucous fibrosis, we determined their diffusion kinetics through human buccal and vaginal mucosa. Four clinically healthy vaginal mucosa specimens (mean patient age± standard deviation: 47±15 years; age range: 31–60 years) and 4 buccal mucosa specimens from 2 male patients and 2 female patients (mean patient age±standard deviation: 31±9 years; age range: 17–53 years) were obtained during surgery. In vitro flux rates of reduced arecoline and arecaidine (r‐arecoline and r‐arecaidine) were determined by use of a flow‐through diffusion apparatus. Analysis of variance, a Duncan multiple range test, and an unpaired t‐test were used to determine steady state kinetics and flux differences over time intervals. Although statistically significant differences were observed between flux values for both alkaloids and tissues at certain time points, these were not considered to be of biological (clinical) significance. However, the flux rates across both mucosa of r‐arecoline were significantly higher statistically than those of r‐arecaidine. The findings demonstrated the differences in the diffusion kinetics between r‐arecoline and r‐arecaidine across human buccal and vaginal mucosa, an observation that could be explained in terms of their ionisation characteristics. Additionally, the results obtained further support the hypothesis that human vaginal mucosa can be used as a model for buccal mucosa in studies of permeability to various chemical compounds.
Oral Candida in HIV‐infected heterosexuals and intravenous drug users in Thailand
Authors: Nittayananta Wipawee , Jealae Sureerath , Winn Than
Published: March 2003

The objectives of this study were to determine levels of oral yeasts in Thai people at different stages of HIV infection compared with HIV‐negative controls, to identify factors associated with the levels of oral Candida, and to determine whether the levels of the organism can be used as a predictive clinical marker in HIV‐infected individuals. One hundred and eighty HIV‐infected heterosexual persons and intravenous drug users (IVDUs) were enrolled (152 men, 28 women). Eighty‐three HIV‐free subjects from the same population were included as controls (48 men, 35 women). Oral yeasts were isolated in 103 HIV‐infected subjects (57.2%) and 36 HIV‐negative controls (43.3%). The mean number of colony forming units (CFU) of oral Candida in the first group was 1.9×104 CFU/ml (range 2.2×102−4.0×106 CFU/ml), which was significantly different statistically when compared with 1.7×103 CFU/ml (range 4.0×102−1.2×105 CFU/ml) in the control group (P=0.0000). The following factors are significantly associated statistically with the levels of oral Candida among the subjects (P<0.05): age, stage of HIV infection, total number of lymphocyte cell count, risk group, nutritional status, general health status, weight loss, type of oral lesions and number of oral lesions and number of sites affected. The study revealed that HIV serostatus, stage of HIV infection, and the occurrence of oral lesions among HIV‐infected subjects may be predicted by the levels of oral Candida (P<0.05). By using a cut‐off point of 2.0×103 CFU/ml, the sensitivity and predicitve values of the level of oral Candida on the HIV serostatus was higher than that based on the culture positivity results alone, although the specificity was similar. These findings suggest that, in conjunction with some other clinical signs and laboratory findings, the levels of oral Candida may be used as a predictive marker of disease in HIV infection.
High risk human papillomavirus in oral squamous carcinoma: evidence of risk factors in a Venezuelan rural population. Preliminary report
Authors: Premoli‐De‐Percoco G. , Ramirez J. L.
Published: March 2003

Abstract: In a search for the presence of human papillomavirus (HPV) and some etiologic cofactors in oral squamous cell carcinoma (OSCC), 50 women diagnosed as OSCC were analyzed by a multiplex polymerase chain reaction (PCR) assay specific for HPV types 6, 11, 16, and 18. This study revealed that 60% (30/50) of the OSCC patients were positive for HPV‐DNA sequences. This group was analyzed according to smoking, alcohol consumption, number of pregnancies, poor oral health and low social economic status. The current results indicate an increased incidence of HPV malignant types in the oral cavity in women with OSCC. Also, they support a multifactorial model of oral cancer causation.
Reproducibility of biopsy grade in Sjögren’s syndrome
Authors: Al‐Hashimi Ibtisam , Wright John M. , Cooley Charles A. , Nunn Martha E.
Published: March 2003

Abstract: The purpose of this study was to examine the reproducibility of biopsy grades at various tissue depths in Sjögren’s syndrome. The biopsy grades of 38 minor salivary gland biopsies were examined at 6 μm, 50 μm, 100 μm, 150 μm, 200 μm, and 250 μm tissue depths. Tissue sections were stained with routine hematoxylin and eosin, graded I–IV, and compared with the initial “baseline” biopsy grade. The majority of the biopsies showed a wide range of grade variability at all depths. No tissue depth was consistently reproducible for any grade (P0.41, 0.64, 0.91, and 0.20, respectively). The difference between baseline grades and grades of deeper sections was sufficient to impact the diagnosis of Sjögren’s syndrome in approximately 60% of the biopsies (P<0.001). The overall result of this study suggests that examination of multiple sections of minor salivary gland biopsies is advisable to improve the reliability of the grade when evaluating Sjögren’s syndrome.
Mutations of the adenomatous polyposis coli gene in areca quid and tobacco‐associated oral squamous cell carcinomas in Taiwan
Authors: Kok Sang‐Heng , Lee Jang‐Jaer , Hsu Hey‐Chi , Chiang Chun‐Pin , Kuo Ying‐Shiung , Kuo Mark Yen‐Ping
Published: March 2003

Background:  Adenomatous polyposis coli (APC) gene mutations have been demonstrated not only in colorectal tumors but also in a variety of human cancers.

Methods:  To elucidate the possible roles of APC gene mutations in oral squamous cell carcinomas (OSCCs), we examined 40 untreated human primary OSCCs using polymerase chain reaction–single strand conformation polymorphism (PCR–SSCP) and DNA sequencing assays.

Results:  By screening nearly one‐half of the coding region (codons 279–1673, including the MCR) of the APC gene, five missense mutations and a 1‐base pair deletion were detected in five (12.5%) tumors, resulting in five amino‐acid substitutions or a truncation of the APC protein. All patients with APC mutations were both areca quid chewers and tobacco smokers (P = 0.049).

Conclusions:  These results suggest that APC mutations may also contribute to the carcinogenesis of at least some OSCCs in Taiwan, especially for the users of areca quid and tobacco.
Genetic polymorphism of cytochrome P4501A1 and susceptibility to oral squamous cell carcinoma and oral precancer lesions associated with smoking/betel use
Authors: Kao Shou‐Yen , Wu Cheng‐Hsien , Lin Shu‐Chun , Yap Soon‐Kiong , Chang Che‐Shoa , Wong Yong‐Kie , Chi Lin‐Yang , Liu Tsung‐Yun
Published: March 2003

Background:   The importance of the CYP1A1 polymorphisms at exon 7 (Ile/Val) and 3′‐untranslated region (3′‐UTR) has been controversial in oral squamous cell carcinoma (OSCC) or head and neck SCC (HNSCC) denoting the value of exploring the correlation between these polymorphisms and risk of betel/smoking associated OSCC. It is also important to evaluate the association between CYP1A1 polymorphisms and susceptibility of oral precancerous lesion (OPL) to confirm the findings in OSCC cases.

Methods:   We examined polymorphic prevalence of CYP1A1 at exon 7 (Ile/Val) and 3′‐UTR in 106 cases with OSCC, 60 cases with OPL, and 146 controls. DNA isolated from surgical specimens and whole blood was used for PCR‐based genotyping.

Results:   The prevalence of the CYP1A1 A/G genotype (Ile/Val) and G/G genotype (Val/Val) in exon 7 of cases with OSCC (79.2 and 7.6%) and OPL (68.3 and 10%) were significantly higher than in controls (53.4 and 1.4%) (P < 0.0001). The novelty of the present study is that we identified the onset age of OSCC in CYP1A1 A/G genotype to be significantly younger than that in A/A genotype (P < 0.01). No significant difference was seen between cases and controls regarding the polymorphisms at 3′‐UTR.

Conclusion:   The findings indicate that the individuals with the CYP1A1 exon 7 containing G allele were at increased risk for OSCC and OPL.
Expression of RANTES and CCR1 in oral lichen planus and association with mast cell migration
Authors: Zhao Z. Z. , Sugerman P. B. , Walsh L. J. , Savage N. W.
Published: March 2003

Background:  T lymphocytes and mast cells infiltrate the lamina propria in oral lichen planus (OLP). Chemokines and their receptors are involved in T cell and mast cell migration and accumulation during the inflammatory process.

Methods:  In the present study, we investigated the role of RANTES and its receptors in OLP using immunohistochemistry, RT‐PCR and an in vitro chemotaxis assay.

Results:  RANTES and CCR1 were expressed on T cells and mast cells in OLP, while OLP lesional T cell supernatants stimulated CCR1 mRNA expression in a human leukemia mast cell line (HMC‐1). TNF‐α stimulated CCR1, CCR4 and CCR5 mRNA expression in the same cell line. OLP lesional T cell supernatants stimulated HMC‐1 migration, which was partly inhibited by anti‐RANTES antibody.

Conclusions:  The present study shows, for the first time, the distribution of RANTES and CCR1 in OLP. It is hypothesized that RANTES and CCR1 may play important roles in mast cell trafficking and related events in OLP.
Involvement of substance P, mast cells, TNF‐α and ICAM‐1 in the infiltration of inflammatory cells in human periapical granulomas
Authors: Kabashima Hiroaki , Nagata Kengo , Maeda Katsumasa , Iijima Tadahiko
Published: March 2003

Background: Substance P (SP), a potent proinflammatory peptide present in sensory neurons, is believed to be a major mediator of neurogenic inflammation. The aim of this study was to examine the localization and involvement of SP, mast cells and tumor necrosis factor‐α (TNF‐α)‐positive cells in human periapical granulomas.

Methods: Sections from seven periapical granulomas were stained using a variety of immunohistochemical methods.

Results: SP‐immunoreactive nerve fibers, mast cells and TNF‐α‐positive cells were found localized in the vicinity of blood vessels in all the samples of periapical granulomas. The vascular endothelial cells stained positively for E‐selectin and intercellular adhesion molecule‐1. SP, TNF‐α‐positive cells and E‐selectin could not be detected in clinically healthy periodontal ligament, and served as a negative control.

Conclusion: Our findings suggest that SP, mast cells, TNF‐α‐positive cells and E‐selectin may modulate the pathogenesis of apical periodontitis and may be responsible for stimulating the formation of granuloma with the resorption of periapical bone.
Sebaceous lymphadenoma of the lip: report of a case of minor salivary gland origin
Authors: Maruyama Satoshi , Cheng Jun , Inoue Tatsuo , Takagi Ritsuo , Saku Takashi
Published: March 2003

A case of sebaceous lymphadenoma occurring in the lip of a 73‐year‐old female is described. The patient had noticed a painless mass in the region of her upper lip for a year. The surgically removed tumor, measuring about 10 mm in diameter, was located just beneath the lip mucosa, expanding into the submucosal and muscle layer. Histologically, the tumor was well encapsulated and consisted of scattered round‐shaped islands of small squamous epithelial cells with focal but apparent sebaceous differentiation in a background of lymphoid stroma. This is the first case report of sebaceous lymphadenoma of minor salivary gland origin.
Successful treatment of invasive stomatitis due to Exophiala dermatitidis in a patient with acute myeloid leukemia
Authors: Myoken Yoshinari , Sugata Tatsumi , Fujita Yoshinori , Kyo Tai‐ichi , Fujihara Megumu , Katsu Masakazu , Mikami Yuzuru
Published: March 2003

Background:  Although the most common orofacial fungal infection in immunocompromised patients is candidosis, infections caused by virulent molds, such as Aspergillus spp. and Furarium spp. are being recognized with increasing frequency. We report a case of oral Exophiala infection in a 39‐year‐old woman with acute myeloid leukemia.

Methods:  Clinical records of the patient were reviewed and the following additional information was collected: histological and microbiological evidence; identification of the causative organism; in vitro antifungal susceptibility.

Results:  The patient developed a necrotic ulcer surrounded by a violaceous rim in the gingiva during neutropenia. Exophiala dermatitidis was identified as the causative organism by histopathological examination and culture, and finally confirmed by sequencing of the ribosomal DNA internal transcribed space domain. In vitro, amphotericin B was found to show strong activity against the Exophiala isolate while itraconazole showed less activity. The patient was successfully treated with parenteral amphotericin B and oral itraconazole in combination with surgical removal of the fungi focus.

Conclusion:  Local excision with adequate antifungal agents can be used to treat immunocompromised patients with Exophiala stomatitis, based on early diagnosis.
Ultrastructural study of synovitis induced by trauma to the rat temporomandibular joint (TMJ)
Authors: Muto Toshitaka , Shigeo Kimiharu , Kanazawa Masaaki , Irie Kazuharu , Yajima Toshihiko , Kaku Tohru
Published: March 2003

Background:  Electron microscopy was used to examine the histologic effect of trauma on the rat temporomandibular joint synovial membrane.

Methods:  Trauma to the TMJ in male Wister rats (100–200 g) was introduced through repeated forced condylar hypermobility. Ultrastructural observations were made 5 days and 6 weeks after the trauma.

Results:  The early response of the synovial membrane was synovial hyperplasia, type A synovial cell loss, dilation of the r‐ER in the type B synovial cells and fibrin deposition on the synovial surfaces. The late response included degeneration of synovial cells with swollen mitochondria and cell projections, and cell fragmentation. Large amount of fibrin deposition on opposing surface layers was also noticed.

Conclusion:  The type A cell loss and fibrin deposition followed by the occurrence of fibrinous materials at opposing surface layers of the synovial membrane suggest that traumatic synovitis causes synovial adhesions.
Induction of Melanogenesis by Tetradecanoylphorbol‐13 Acetate and Endothelin 3 in Embryonic Avian Peripheral Nerve Cultures
Authors: NATAF VALÉRIE , LE DOUARIN NICOLE M.
Published: March 2003

In this study, we have analyzed the melanogenic potential of Schwann cells using in vitro cell cultures of embryonic quail peripheral nerves. It is shown that in Schwann cells, two factors, 12‐O‐tetradecanoylphorbol‐13 acetate (TPA) and endothelin 3, trigger a differentiation pathway toward melanocytes, and that Steel factor has no effect on these cells unless treated simultaneously with TPA. In these cultures, TPA induces the expression of c‐kit, whereas Steel factor enhances the development of melanocytes. In the assay system we employed, neither neuronal nor catecholaminergic phenotypes were obtained, regardless of various combinations of related factors added to the culture medium. These data support our previous observations indicating the existence of bipotent progenitors that are capable of differentiating into Schwann cells or into melanocytes, and the regulatory role of endothelin 3 on those precursors, as revealed by the clonal culture of neural crest cells.