Discordant patient-physician assessments of disease activity and its persistence adversely impact quality of life and work productivity in US Hispanics with rheumatoid arthritis.

OBJECTIVE: This study was designed to evaluate the determinants of patient and physician global assessments (PtGA and MDGA, respectively) of disease activity, their discordance and change over 2 years in Hispanics with rheumatoid arthritis (RA). We further examined the impact of discordance and its persistence on health-related quality of life (HRQOL) and work productivity on final visit. METHODS: We studied 536 Hispanics with established RA from a single centre. PtGA and MDGA were measured annually on 10 cm visual analogue scales and discordance was defined as absolute difference between them ≥3 cm. Associations between predictors and outcomes of interest were evaluated using multivariable regression and analysis of covariance for cross-sectional and longitudinal data, respectively. RESULTS: Independent predictors of baseline PtGA were pain, fatigue, depression, general health perceptions and tender joint count. MDGA was predicted by swollen joint count, tender joint count, erythrocyte sedimentation rate, fatigue and depression. Both PtGA and MDGA improved over time (all p<0.001). Discordance was observed in 43% at baseline, with fair stability over 2 years. Higher (worse) patient ratings were most prevalent; their presence at any time and increasing persistence predicted lower physical and mental HRQOL, decreased work productivity and more activity impairment at 2-year follow-up (all p<0.001). CONCLUSIONS: Determinants of PtGA, MDGA and changes over 2 years were disparate in Hispanics with RA yielding significant discordance. Higher patient ratings at any time contributed to worse HRQOL, work productivity and activity impairment on final visit.

Preliminary results on organization on the court, physical and technical performance of Brazilian professional futsal players: comparison between friendly pre-season and official match

The main aim of this study was to verify possible differences between a friendly pre-season match (FM) and an official in-season match (OM) regarding physical, technical, and organizational performances of a professional Brazilian futsal team. Ten professional futsal athletes participated in this study. The matches were monitored with video cameras (30 Hz) and athlete trajectories obtained with automatic tracking. The values obtained for distance covered per minute, percentage of distance covered at moderate intensity, team coverage area, spread, passes, possessions, ball touches and successful passes per minute were greater for the OM than FM. On the contrary, percentage of distance covered, standing and walking was greater for the FM than OM. We concluded that physical, technical, and tactical performances are different between a FM and an OM in futsal and also these parameters mutually influenced each other distinctly. Future studies should verify whether pre-season tournaments reproduce similar demands to a regular season official match

Putative classification of clades of enterohemorrhagic Escherichia coli O157 using an IS-printing system.

UNLABELLED: Enterohemorrhagic Escherichia coli O157 (O157) strains can be classified in clades by single nucleotide polymorphisms (SNPs), but this analysis requires significant laboratory effort. As the distribution of insertion sequence (IS) 629 insertions has been reported to be biased among different clades, O157 isolates can be putatively classified in clades by comparison with an IS629 distribution database. A database of the IS629 distribution in O157 strains isolated in Chiba Prefecture and their classification in clades was determined by SNP analysis and IS-printing, an easy and quick analytical tool for IS629 in the O157 genome. The IS629 distribution in O157 strains isolated in Fukuoka and Yamagata Prefectures was determined by IS-printing. These strains were putatively classified in clades by Relative Likelihood calculations that compared the IS-printing data and the IS629 distribution database. Concordance Ratios were calculated, which compared the number of strains putatively classified in a clade by Relative Likelihood to the number of strains classified in that clade by SNP analysis. For the Fukuoka and Yamagata strains, the Concordance Ratios for clades 3, 6 and 8 were 97-100%, for clade 7 about 88%, and for clades 2 and 12 over 90%. In conclusion, O157 clade 2, 3, 6, 7, 8 and 12 strains could be putatively classified by IS-printing. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated that enterohemorrhagic E. coli O157 (O157) strains could be putatively classified in clades using an IS-printing system. IS-printing was previously developed as a relatively quick and easy tool for analysis of insertion sequence 629 in the O157 genome. Since most local government public health institutes in Japan carry out IS-printing for early detection of O157 outbreaks, these data should be useful for putative classification of O157 strains in each area.

Analysis of the population genetics of clades of enterohaemorrhagic Escherichia coli O157:H7/H- isolated in three areas in Japan.

AIMS: The genetic differences of enterohaemorrhagic Escherichia coli O157 (O157) strains isolated from humans in three widely-separated areas in Japan were analysed to provide information on possible geographic aspects of O157 pathogenicity. METHODS AND RESULTS: Epidemiologically unlinked O157 strains were isolated in Chiba (300 strains), Fukuoka (260 strains) and Yamagata (81 strains) prefectures. These strains were classified in clades by single nucleotide polymorphism in seven loci and lineage-specific polymorphism assay-6, and differences between the strains in each clade were compared by population genetic analyses using the IS-printing system. Analysis of the clades from the three areas showed linkage disequilibrium of the strains in each clade. Comparison of the genetic differences of strains from the three areas in each clade, from calculated ΦPT values, indicated that the strains in each clade were the same population in all three areas, except possibly the clade 12 strains. CONCLUSIONS: Population genetics analyses confirmed that the distribution of O157 strains in the clades isolated in three areas in Japan were similar and stable. SIGNIFICANCE AND IMPACT OF THE STUDY: The pathogenicity of O157 strains infecting humans was comparable due to the similar, stable geographic distribution of O157 clades.

What is the effect of compression garments on a balance task in female athletes?

OBJECTIVES: To investigate the effect of long leg compression garments on the postural sway and balance ability of female athletes at a state sports institute. DESIGN: A laboratory was set up to analyse kinetic and kinematic variables using a double blind, randomised controlled repeated measures cross over design. METHOD: Participants were required to perform a single leg balance task for up to 60s across six conditions; including eyes-open and eyes-closed while wearing conventional shorts (control), loose-fitted compression garment and well-fitted compression garments. Simultaneous measurements of ground reaction forces and full body joint kinematics were recorded. Postural stability was assessed by measuring the overall stabilisation time as well as the movement of the centre of pressure (CoP) and centre of mass (CoM) from baseline measures. RESULTS: During one leg stance, significantly greater postural stability (p < 0.01) was observed with eyes open vs eyes closed, irrespective of compression group. A significantly greater (p < 0.05) balance time was observed with eyes closed when wearing well-fitted compression garments compared to conventional shorts. Differences were not present with use of the loose-fitted garment. Additionally, a significant interaction effect between compression condition and vision was observed analysing the variation about the sway (swaySD) of the CoP and CoM data (p < 0.05). The interaction effect revealed greater variability of movement with eyes closed as participants' level of compression decreased. No significant differences were observed with eyes open. CONCLUSIONS: The difficulties of postural stability while maintaining the single leg stance wearing conventional shorts were improved with use of the well-fitted compression garments (in the eyes-closed condition). Proper fitted compression garments may be beneficial for injury management and injury prevention.

Lipid infiltration in the parotid glands: a clinical manifestation of metabolic syndrome.

BACKGROUND: The clinical features of lipid infiltration in the parotid glands (LIPG) have not been studied. Monitoring of atomic-bomb survivors for late effects of radiation exposure has provided the opportunity to review the clinical findings of LIPG. METHODS: A total of 992 atomic-bomb survivors in Nagasaki, Japan underwent lachrymal and salivary secretion tests and anthropometric, biochemical, and abdominal ultrasonographic examinations between 2002 and 2004. Among 465 subjects who had reduced tear and/or salivary excretion, 176 subjects took a salivary magnetic resonance imaging (MRI) examination. RESULTS: LIPG was detected in 53 of the 176 subjects who had salivary MRI. LIPG cases showed a preponderance of females and fatty liver compared with the subjects without LIPG. Age-and-sex-adjusted regression analysis revealed that body mass index (BMI), low-density lipoprotein cholesterol, triglycerides, hemoglobin A1c, and C-reactive protein were higher, whereas high-density lipoprotein cholesterol and adiponectin were lower, in the subjects with LIPG. Multivariate logistic regression analysis showed that BMI and fatty liver were mutually associated with LIPG independently from radiation dose. CONCLUSIONS: LIPG associated with BMI, fatty liver, and coronary risk factors was a clinical manifestation of metabolic syndrome.

Parasite infection and sand coarseness increase sand crab (Emerita analoga) burrowing time.

Parasites with indirect life cycles require trophic transmission from intermediate hosts to definitive (vertebrate) hosts. Transmission may be facilitated if parasite infection alters the behavior of intermediate hosts such that they are more vulnerable to predation. Vulnerability to predation may also be influenced by abiotic factors; however, rarely are the effects of parasites and abiotic factors examined simultaneously. The swash zone of sandy beaches is a particularly harsh environment. Sand crabs (Emerita analoga) burrow rapidly in the swash zone to avoid predators and dislodgment. We examined prevalence and abundance of the acanthocephalan parasite Profilicollis altmani in sand crabs, and investigated the synergistic effects of sand grain size (an important abiotic factor), parasite infection, body size and reproductive condition on burrowing speed in females, from three California sites. More heavily parasitized crabs burrowed more slowly, making them potentially more vulnerable to predation by marine bird definitive hosts. Ovigerous females harbored more parasites than non-ovigerous females, but burrowed more quickly. All crabs burrowed slowest in the coarsest sand, and burrowing times increased with repeated testing, suggesting that it is energetically costly. Abiotic and biotic factors influence burrowing, and behavioral variation across sites may reflect the response to natural variation in these factors.

Time-motion analysis of international and national level futsal.

Futsal is the Fédération de Internationale Football Association's officially recognized five-a-side indoor soccer, which although increasing in popularity worldwide, lacks the Australian or other English language research necessary to enable the growth of the sport. The purpose of this study was to establish a comprehensive overview of the demands of futsal by a time-motion analysis on 8 Australian National Team players and 10 State League Team players over 4 futsal matches. The study analyzed 6 locomotor activity categories, focusing on total distance covered, total duration of activities, total frequency of activities, effort distance, and effort duration. The national team covered a 42% greater overall distance than the state league team. In terms of relative data normalized for match duration, only the standing duration value was significantly different between the teams. Furthermore, futsal players of elite and subelite level in Australia perform a change in activity every 8-9 seconds on the court, and the national team athletes attained a higher, yet nonsignificant, average match-play velocity. This may be because of the national futsal athletes participating in an extended game duration, potentially suggesting that higher levels of competition facilitate a higher intensity of match play and greater physiological demands on individual players. Apart from the differences in timing structure and overall metabolic work, there was no real difference between the levels of competition within the Australian futsal analysis, although at higher levels of competition, there may be a need for more recovery because of the elevated intensity of the match. When comparing the data with other countries, however, Australian futsal players produce less distance and duration than Spanish futsal players.

The reliability and validity of subjective notational analysis in comparison to global positioning system tracking to assess athlete movement patterns.

Subjective notational analysis can be used to track players and analyse movement patterns during match-play of team sports such as futsal. The purpose of this study was to establish the validity and reliability of the Event Recorder for subjective notational analysis. A course was designed, replicating ten minutes of futsal match-play movement patterns, where ten participants undertook the course. The course allowed a comparison of data derived from subjective notational analysis, to the known distances of the course, and to GPS data. The study analysed six locomotor activity categories, focusing on total distance covered, total duration of activities and total frequency of activities. The values between the known measurements and the Event Recorder were similar, whereas the majority of significant differences were found between the Event Recorder and GPS values. The reliability of subjective notational analysis was established with all ten participants being analysed on two occasions, as well as analysing five random futsal players twice during match-play. Subjective notational analysis is a valid and reliable method of tracking player movements, and may be a preferred and more effective method than GPS, particularly for indoor sports such as futsal, and field sports where short distances and changes in direction are observed.

Nosocomial outbreak of epidemic keratoconjunctivitis accompanying environmental contamination with adenoviruses.

An outbreak of acute keratoconjunctivitis involving 27 patients occurred in the Department of Ophthalmology, Kurume University Hospital. Adenoviral DNA was detected in four inpatients, one outpatient and one healthcare worker. Sequence-based typing of adenoviral DNA indicated serotype 3 from one inpatient, the rest being serotype 37. At a later stage of the outbreak adenoviral DNA types 37 and/or 3 were also detected from almost all environmental instruments and commonly used eye drops, despite thorough disinfection of the environment and enforcement of various infection control measures. The detection rate of adenoviral DNA in environmental swabs was 81%. A further second disinfection of the environment reduced the detection rate of adenoviral DNA to 38%. The outbreak ceased after closing the ophthalmology ward and outpatient consulting room, accompanied by enhanced cleaning of environmental instruments and the introduction of disposable eye drops for individual patients.

Murine strain differences in 8-hydroxy-deoxyguanosine formation in hepatic DNA induced by oxidized lard and dietary oils.

Difference of 8-hydroxy-deoxyguanosine (8-OH-dG) formation in liver DNA in C3H/HeN and in C57BL/6 mice--fed oxidized lard and dietary oils (soybean and sardine)--was investigated. The blank levels of 8-OH-dG were higher in C3H/HeN mice (highly sensitive to liver tumorigenesis) than in C57BL/6 mice (resistant strain). The level of 8-OH-dG increased much more in C3H/HeN mice than in the C57BL/6 mice fed by oxidized lard and dietary oil treatment. Feeding oxidized lard and dietary oils increased 8-oxo-guanine DNA glycosylase I (OGG1) and mRNA 8-oxo-dGTPase in C57BL/6 mice. On the other hand, no appreciable change of mRNA in the C3H/HeN mice was observed. The formation differences of 8-OH-dG from the two murine strains fed with oxidized lard and dietary oils may be associated with the different mRNA levels in the DNA repair enzymes because the mRNA levels in the DNA repair enzymes were much lower in C3H/HeN mice than in C57BL/6 mice.

Validity of mutagenic activity as an indicator of river water pollution.

OBJECTIVES: To investigate if mutagenicity could be expressed by known water pollution indicators, we determined the mutagenic activity of blue rayon extracts from sampled river water with the Ames test utilizing new strains of bacteria, and compared the results with those of known indicators of water pollution. METHODS: Water samples were collected by the blue rayon adsorption method at sixteen sites in six rivers in the North Kyushu district. The Assay of mutagenicity was carried out using the Ames test. The test strains wereSalmonella typhimurium TA100, YG1024, YG1041 and YG1042. B(a)P, Trp-P-1 and Trp-P-2 were quantified by HPLC. Determinations of SS, BOD, COD, T-N, T-P, DOC, and A(260)/DOC were performed. RESULTS: The extracts from five sampling sites showed higher mutagenicity toward strain YG1024 with or without S9mix, and the extracts from two of these five sites showed higher mutagenicity toward strain YG1041 with and without S9mix. However, the water pollution indicators did not show specific trends that were consistent with the mutagenic activity. CONCLUSIONS: Since the mutagenic activity of river water could not be predicted using known water pollution indicators, we recommend that biological examinations such as mutagenicity tests be added to the indicators that are currently in use.

The mutagenicity of amino-derivatives of diphenyl ether herbicides in new Salmonella typhimurium YG tester strains.

In this study, we examined the mutagenicity of four diphenyl ether herbicides and their amino derivatives in Salmonella typhimurium TA tester strains and YG tester strains. YG tester strains have been newly developed for sensitive detection of specific chemicals. S. typhimurium YG 1021, YG 1024, YG 1026 and YG 1029 strains are sensitive to mutagenic nitoroarenes and hydroxyamines. S. typhimurium YG 3003 is a strain that is sensitive to some oxidative mutagens. And S. typhimurium YG 7108 is useful for detection of mutagenic alkylating agents. As a result, each amino derivative of diphenyl ether herbicides is more mutagenic than its parent herbicide in S. typhimurium TA and YG tester strains with metabolic activation by S9 mixture. Moreover, S. typhimurium YG tester strains are more useful for highly sensitive detection of mutagens than S. typhimurium TA tester strains. We also examined the production of amino derivatives in a water environment from parent herbicides. It was clear that diphenyl ether herbicides rapidly transform to amino derivatives in a water environment.

Isolation and characterization of Desulfitobacterium sp. strain Y51 capable of efficient dehalogenation of tetrachloroethene and polychloroethanes.

A strict anaerobic bacterium, strain Y51, was isolated from soil contaminated with tetrachloroethene (PCE). Strain Y51 is capable of very efficiently dehalogenating PCE via trichloroethene (TCE) to cis-1,2-dichloroethene (cis-1,2-DCE) at concentrations as high as 960 microM and as low as 0.6 microM. Strain Y51 was gram-negative, motile with some lateral flagella, and curved rod-shaped. On the basis of the 16S rDNA sequence, the organism was identified to be a species within the genus Desulfitobacterium. Strain Y51 also had dehalogenation activities toward polychloroethanes such as hexa-, penta-, and tetrachloroethanes, from which dichloroethenes were produced as the final products. The cell extracts mediated the dehalogenation of PCE with reduced methyl viologen as an electron carrier at the specific rate of 5.0 nmol min(-1) mg cell protein(-1) (pH 7.2, 37 degrees C). Dehalogenation was highly susceptible to air oxidation, and to potential alternative electron acceptors such as nitrite or sulfite.

Fas/FasL mediated apoptosis of thyrocytes in Graves' disease.

We examined in the present study the possible involvement of Fas and its ligand (FasL) in the process of Graves' disease. Immunohistochemical analysis showed that few normal thyrocytes expressed Fas but many thyrocytes in Graves' disease expressed this molecule. The percentage of FasL-positive thyrocytes in Graves' thyroids was, however, less than in normal thyroids. Several apoptotic thyrocytes and infiltrating mononuclear cells (MNCs) were detected scattered throughout Graves' thyroid tissues and abundant proliferating cell nuclear antigen (PCNA)-positive thyrocytes were present. Apoptotic cells, as well as PCNA-positive cells, were scarcely detectable in normal thyroid glands, however. In vitro treatment of thyrocytes by IL-1beta a cytokine found to be expressed in Graves' thyroid glands, increased Fas but reduced FasL expression. IL-1beta-stimulated thyrocytes became sensitive to apoptosis by anti-Fas IgM monoclonal antibody (mAb). Activated T cells, which strongly expressed FasL, showed cytotoxic activity toward IL-1beta-stimulated thyrocytes but not toward unstimulated thyrocytes. This cytotoxic activity involved the Fas/FasL pathway. Importantly, unstimulated thyrocytes could kill activated, but not resting, T cells. IL-1beta-stimulated thyrocytes, with down-regulated FasL expression, could not efficiently kill activated T cells. The cytotoxic activity of unstimulated thyrocytes toward activated T cells was inhibited by anti-FasL mAb. Interestingly, unstimulated thyrocytes induced apoptosis in IL-1beta-stimulated thyrocytes but not in unstimulated thyrocytes. These interactions were also blocked by anti-FasL mAb. Our results suggest that the apoptotic cell death of both thyrocytes and infiltrating MNCs found in Graves' thyroid glands is regulated by IL-1beta through Fas/FasL interactions.

Pulmonary nocardiosis associated with idiopathic thrombocytopenic purpura.

A 69-year-old woman with idiopathic thrombocytopenic purpura, who was regularly followed and treated with prednisolone and danazol, was admitted to our hospital because of shortness of breath. Chest roentgenogram showed a large amount of left-sided pleural effusion. Gram-positive branching rods, subsequently identified as Nocardia farcinica, were isolated from the fluid. Antibiotic treatment together with pleural drainage with an intercostal catheter resulted in complete remission of pyothorax. Pulmonary nocardiosis is a rare disease, but recognition of the disease in immunocompromised patients and the prompt initiation of appropriate treatments based on isolation of the pathogen can lead to a successful outcome.

Micronucleus induction and chromosomal aberration of 1- and 3-nitroazabenzo[a]pyrene and their N-oxides.

Nitro-azabenzo[a]pyrenes, 1- or 3-nitro-azabenzo[a]pyrene and their N-oxides are nitrated derivatives of azabenzo[a] pyrene (ABP) containing nitrogen in the 6-position of benzo[a]pyrene (B[a]P). The nitro-ABP-N-oxides (ABPOs) were formed by reaction of ABP with excess HNO(3). These derivatives were noteworthy as potent mutagens for Salmonella strains, and were present in fine particles of diesel particulates. In this study, micronucleus induction in mice and chromosomal aberrations due to means of Chinese hamster lung fibroblast (CHL) cells were investigated to determine genotoxicity in order to define the relationship with the mutagenic potency of these derivatives. The induction of micronucleus polychromatic erythrocytes (MNPCEs) was dependent on the dose response of 10-40 mg for 3-N-6-ABP, and of 10-40 mg for 1-N-6-ABP, and in addition, 1- and 3-N-6-ABPOs markedly induced MNPCEs in a dose range of 10-400 mg and from 1 to 80 mg, respectively, when the compound was intraperitoneally administrated in two mice at each dose. The results show that of the four compounds, 3-N-6-ABPO demonstrated a marked increase in MNPCES: On the other hand, chromosomal aberrations of the four compounds were investigated by the duplicate tests using CHLS: The results after a 48 h treatment induced aberrations of the chromatid type, chromatid breaks and exchanges for 1- and 3-N-6-ABP, and mainly chromatid exchanges for 1- and 3-N-6-ABPO. The frequency of chromosomal aberrations associated with nitro substitution on the ABPO structure. Chromosomal aberrations of nitro derivatives of ABPO substituted at the 3-position on the structure were more potent than those at the 1-postion. N-oxide derivatives have been found to be reduced to anion radicals much more easily than azaB[a]P and its nitro derivatives. This suggests that the electrochemical reduction of the chemicals plays an important role in the metabolic activation of nitrated B[a]P derivatives.

Elevation of serum pro-gastrin-releasing peptide in patients with medullary thyroid carcinoma and small cell lung carcinoma.

Medullary thyroid carcinoma (MTC) arises from parafollicular or C cells of the thyroid gland and produces a variety of peptides such as calcitonin (CT) and gastrin-releasing peptide (GRP). Here we measured serum levels of pro-gastrin-releasing peptide (Pro-GRP), a more stable precursor of GRP, in 15 patients with MTC (4 males, 11 females) who did not show any clinical or radiologic signs of small cell lung cancer. Serum Pro-GRP levels were elevated in 80% (12/15) patients. Significant correlation was observed between serum Pro-GRP and CT (r = 0.52) and carcinoembryonic antigen (CEA) (r = 0.56). Serum Pro-GRP levels also correlated with tumor size (r = 0.70). Serum Pro-GRP levels also decreased below the cut-off range in one patient after surgical resection. Our data suggest that Pro-GRP, which is considered to be a specific marker for small cell lung carcinoma, seems to be also helpful and additional marker for the diagnosis and monitoring the response to therapy in patients with MTC in addition to calcitonin as the main tumor marker.

Anaplastic changes associated with p53 gene mutation in differentiated thyroid carcinoma after insufficient radioactive iodine (131I) therapy.

Thirty-two patients with differentiated thyroid carcinomas with distant metastasis were examined using a radioactive iodine (131I) tracer dose prior to 131I therapy and followed up for 10 years or until death (whichever occurred first). Nineteen patients who received 131I therapy had an accumulation of 131I in the metastases (group I) and 15 of those patients were alive more than 10 years after the first 131I treatment. In contrast, all 13 patients in whom the metastases did not show accumulation of 131I died within 10 years. Of the latter group, eight patients had received 131I therapy (group II), four of whom died with anaplastic changes within 5 years of treatment. p53 gene mutation was identified by immunohistochemistry in primary thyroid carcinoma tissue from patients with anaplastic changes that were evident during total thyroidectomy. Five patients did not receive 131I therapy (group III), of whom one, who also had a p53 gene mutation in the original tumor, died with anaplastic change 10 years after thyroidectomy. Seven patients in group I had p53 gene mutations in their thyroid carcinoma tissues, but none showed anaplastic changes. Our results suggest that 131I therapy may be useful for patients with distant metastases, with or without p53 gene mutations, which show accumulation of 131I from tracer and therapeutic doses. In contrast, 131I therapy is apparently not effective in patients who do not show sufficient accumulation of 131I, but rather, may cause early anaplastic changes with a p53 gene mutation.

Etidronate inhibits human osteoblast apoptosis by inhibition of pro-apoptotic factor(s) produced by activated T cells.

Humoral factors produced by activated T cells are thought to be important in the development of bone loss in patients with rheumatoid arthritis (RA). We investigated the inhibitory effect of etidronate disodium (EHDP) on apoptosis of human osteoblasts induced by supernatants from in vitro activated T cell cultures. Human osteoblastic cell line MG63 cells and human primary osteoblast-like cells were used in the present study as human osteoblasts. T cells were incubated with interleukin-2 and further activated with 1 2-o-tetradecanoyl-phorbol 13-acetate and ionomycin, either in the presence or absence of EHDP. After we carried out the cultivation, we examined the cytotoxicity of cultured T cell supernatants toward MG63 cells and human primary osteoblast-like cells. Supernatants from activated but not resting T cell cultures efficiently induced apoptosis of MG63 cells and primary osteoblast-like cells. Supernatants from activated T cell cultures, incubated with EHDP, exhibited significantly less cytotoxicity than did supernatants incubated in the absence of EHDP. In contrast, the cytotoxicity of activated T cell culture supernatants was not affected by direct treatment of human osteoblasts with EHDP. The concentration of soluble Fas ligand in activated T cell culture supernatants was actually increased by EHDP. However, EHDP did not influence soluble Fas and tumor necrosis factor-alpha concentrations in the supernatant. Furthermore, treatment of human osteoblasts with EHDP did not alter their expression of Bcl-2/Bcl-xL or their sensitivity to anti-Fas immunoglobulin M-induced apoptosis. Our results suggest that EHDP inhibits the production of soluble factor that induces apoptosis of human osteoblasts and thus exhibits a protective action toward human osteoblast apoptosis induced by activated T cell culture supernatants. Although the exact EHDP-regulated molecule that induces apoptosis of human osteoblasts is unknown at present, our study may explain part of the therapeutic action of bisphosphonates in RA complicated by bone loss.