Identification by whole-exome sequencing of new single-nucleotide polymorphisms associated with molar-incisor hypomineralisation among the Lebanese population.

OBJECTIVE: Molar-incisor hypomineralization (MIH) is a developmental qualitative enamel defect, causing a worldwide challenging dental problem. The etiology of this defect remains unclear. Here we identify by whole-exome sequencing (WES) new single-nucleotide polymorphisms (SNPs) in genes expressed during enamel mineralization and in those modulating prenatal, natal and postnatal risk factors among the Lebanese MIH children: immune system and xenobiotic detoxification. DESIGN: Dental examination for MIH was performed based on the MIH index for diagnostic criteria. Saliva samples were collected from 37 non-related, MIH-diagnosed subjects for DNA extraction. WES was performed on the Illumina HiSeq2000 platform. The χ2 test and Fisher's exact test were used to determine relationship between SNPs frequencies and MIH. OR and its 95% CI were used to report the strength of association. The significance threshold was set at 0.05. RESULTS: Among the Lebanese population, 37 SNPs presented a significant association with MIH in the following genes: AMTN, MMP-20, STIM1, STIM2, ORAI1, SLC34A2, SLC34A3, VDR, PVALB, HSP90B1, TRPM7, SLC24A4, CA6, SLC4A2, TNFRSF11A, IL10RB, ARNT, ESR1 and CYP1B1. CONCLUSION: This is the first WES study conducted in patients with MIH. Yet, interactions between polymorphisms in different gene categories are to be investigated for a better assessment of MIH susceptibility.

Relation between molar-incisor hypomineralization (MIH) occurrence and war pollutants in bombarded regions: Epidemiological pilot study in Lebanon.

BACKGROUND: Molar-incisor hypomineralization (MIH), a developmental enamel defect affecting one or more first permanent molars (FPMs) and sometimes incisors (PIs), is one of the most common pandemic health problems in the world. MIH etiology is still unclear and has been suggested to be related to exposure to environmental toxicants during enamel mineralization. AIMS: To assess the susceptibility to MIH occurrence in regards to war pollutants through the investigation of the prevalence and the clinical characteristics of MIH in a group of Lebanese children whose FPMs and PIs enamel mineralization coincides with the 2006 Lebanese war. PATIENTS AND METHODS: This cross-sectional study was performed in schools from different regions of Lebanon. Schoolchildren born in 2004, 2005, 2006, and 2007 were examined for MIH. Clinical status, lesion type, extension, and severity were recorded using the short form chart of the MIH index. Pearson's Chi-square or Fischer's exact test were used to determine if there is a significant relationship between categorical variables. RESULTS: An overall MIH prevalence of 22.93% has been reported. Forty-seven point seventy-five per cent had both molars and incisors affected. Demarcated opacities were the most frequently observed clinical status. Most of the MIH FPMs and PIs were mildly affected with lesions extended on less than the third of the tooth surface. CONCLUSIONS: MIH prevalence among children born around 2006 Lebanese war is high. The hypothesis of a relation between MIH susceptibility and war pollutants in bombarded regions is legible but requires to be elucidated via additional in vitro and in vivo studies for accurate risk assessment.

Molar-incisor hypomineralisation in Lebanon: association with prenatal, natal and postnatal factors.

BACKGROUND: Molar-incisor hypomineralisation is an enamel developmental defect highly prevalent in Lebanon. Literature suggests that perinatal conditions and childhood illnesses might be potential aetiological factors for this affection. AIMS: This case-control study aimed to investigate the association of MIH with prenatal, natal and postnatal factors amongst 7-9 years Lebanese children and to end up with recommendations to overcome its occurrence. METHODS: Self-administered, structured questionnaire including potential etiological factors was distributed to 659 MIH and non-MIH children's parents. The analysis of data was carried out using Statistical Package for Social Sciences Computer Software (SPSS 21.0, Inc., Chicago, IL, USA). For Statistical analysis, Pearson's chi-square, Fischer's exact test and multivariate regression model were used. A p value of less than 0.05 was considered statistically significant. RESULTS: Children whose mothers had consumed food and drinks canned during pregnancy had 2.9 (CI: 1.367 to 6.187) times more likely to have MIH. Those who had history of taking antibiotics had 2.15 (CI: 1.186 to 3.909) times higher odds of MIH than those who did not have while those who had fever episodes during the early childhood years were 2.057 (CI: 1.149 to 3.683) times more likely to develop MIH. CONCLUSION: During early childhood, careful handling of high fever, greater public awareness regarding misuse of antibiotics and education about bisphenol A and how to avoid it during pregnancy and breastfeeding are recommended to decrease the occurrence of MIH.

Molar incisor hypomineralisation in Lebanon: prevalence and clinical characteristics.

BACKGROUND: Molar incisor hypomineralisation (MIH) is a qualitative enamel developmental defect affecting 1-4 first permanent molars and sometimes the permanent incisors. MIH is extremely widespread around the world and presents a considerable clinical problem in paediatric dentistry. Although, little prevalence data exist for Middle East populations including the Lebanese one. AIM: The objectives of this study were to investigate the prevalence of MIH in 7-9-year-old Lebanese children, with relevance to gender, jaw and side distribution, and to assess the clinical status, extent and severity of MIH lesions of the affected teeth. DESIGN: Representative sample (n = 659) of 7-9-year-old Lebanese children attending private and public schools distributed throughout Lebanon was examined for MIH. Clinical status, extent and severity of MIH lesions on FPMs and permanent incisors were scored using the short-form grading method (MIH index) of Ghanim et al. (Eur Arch Paediatr Dent 16:235-246, 2015). RESULTS: An overall MIH prevalence of 26.7% was reported with no significant predilection for girls over boys. 52.8% of the cases present with only molars and. 47.2% with both molars and incisors and did not present any significant difference between upper and lower jaws (P = 0.325). Left-side FPMs were more affected than the right ones (P = 0.0218). Central incisors were significantly more affected than the laterals in both jaws (P < 0.0001). Maxillary central incisors were significantly more affected than their mandibular counterparts (P < 0.0001). Most of the clinical status was demarcated opacities extended on less than the third of the tooth surface. The extent of lesions correlated significantly with the number of affected molars. Most of the affected teeth presented with mild defects and the degree of severity was not correlated with gender but significantly increased with age. CONCLUSIONS: MIH is prevalent in Lebanon. Further studies are required to analyse the possible systemic and environmental etiologies among Lebanese children.

Audio-computer-assisted survey interview and patient navigation to increase chronic viral hepatitis diagnosis and linkage to care in urban health clinics.

Intravenous drug use and sexual practices account for 60% of hepatitis C (HCV) and B (HBV) infection. Disclosing these activities can be embarrassing and reduce risk reporting, blood testing and diagnosis. In diagnosed patients, linkage to care remains a challenge. Audio-computer-assisted survey interview (Audio-CASI) was used to guide HCV and HBV infection testing in urban clinics. Risk reporting, blood testing and serology results were compared to historical controls. A patient navigator (PN) followed up blood test results and provided patients with positive serology linkage to care (LTC). Of 1932 patients surveyed, 574 (30%) were at risk for chronic viral hepatitis. A total of 254 (44.3%) patients were tested, 34 (13.5%) had serology warranting treatment evaluation, and 64% required HBV vaccination. Of 16 patients with infection, seven HCV and three HBV patients started treatment following patient LTC. Of 146 HBV-naïve patients, 70 completed vaccination. About 75% and 49% of HCV antibody and HBV surface antigen-positive patients were born between 1945 and 1965. Subsequently, automated HCV testing of patients born between 1945 and 1965 was built into our hospital electronic medical records. Average monthly HCV antibody testing increased from 245 (January-June) to 1187 (July-October). Patient navigator directed LTC for HCV antibody-positive patients was 61.6%. In conclusion, audio-CASI can identify patients at risk for HCV or HBV infection and those in need of HBV vaccination in urban medical clinics. Although blood testing once a patient is identified at risk for infection needs to increase, a PN is useful to provide LTC of newly diagnosed patients.

Sex prediction from morphometric palatal rugae measures.

While abundant research has been conducted on palatal rugae (PR), the literature pertaining to the sex dimorphism of the palatal rugae and their use for sex prediction is inconclusive. Moreover, palatal rugae have been classified into categories based on length, shape, direction and unification but accurate rugal morphometric linear and angular measurements have not yet been reported. OBJECTIVE: The aims of this study were to -1- assess the dimensions and bilateral symmetry of the first three palatal rugae in an adult population and -2- explore sex dimorphism and the ability to predict sex from palatal rugae measurements. MATERIALS AND METHODS: The maxillary dental casts of 252 non-growing subjects (119 males, 130 females, mean age 25.6 ± 7.7 years) were scanned using a laser system (Perceptron ScanWorks® V5). Angular and linear transverse and anteroposteior measures of the first three palatal rugae were recorded. Independent samples t-tests and paired samples t-tests were used to test for side related differences and sex dimorphism. Multiple logistic regression was employed to model sex using associated palatal rugae measures. RESULTS: Palatal rugae exhibited lateral asymmetry in the majority of bilateral measures. Males presented with larger values for 9 out of 28 parameters. Four linear rugae measurements and one angular measurement together correctly classified 71.4% of the subjects in their true gender. CONCLUSIONS: Morphometric palatal rugae measurements demonstrated promising usefulness in sex prediction. Recording morphometric linear and angular measures is recommended as an adjunct to the commonly used classification based on the shapes of rugae.

Palatal rugae morphology in an adult mediterranean population.

BACKGROUND: The use of the palatal rugae in forensic odontology is based on their unique and individual characteristics. Few studies have assessed the palatal rugae in Mediterranean populations and none in the Lebanese population. OBJECTIVE: Assess the shape and other morphological features of the palatal rugae in a Lebanese adult population, and compare them with reported similar features in other populations. MATERIALS AND METHODS: Rugae characteristics were assessed on the maxillary dental casts of 217 non-growing subjects (95 males, 122 females, age 25.5 ± 7.6 years) according to guidelines established by Thomas and Kotze (1983) and Lysell (1955). The overall number of rugae and numbers of primary rugae (> 5mm in length), secondary rugae (3-5mm) and fragmentary rugae (2-3mm) on either side were recorded. Rugae were classified according to shape, direction and presence of unification. Z-tests were used to compare the proportions between right and left sides and between genders. The mean numbers of rugae in each category were compared with independent samples t-tests between males and females; paired samples t-tests were employed to compare mean numbers of rugae in each category between right and left sides. The data were compared with published reports on other Mediterranean cohorts. RESULTS: The average number of rugae was 7.7 per individual, 3.81 on the right and 3.89 on the left. Curved, wavy and straight rugae patterns were equally common (one third each). The spatial direction of most rugae (49.3%) was backward. Circular, non-specific and convergent rugae were rare (< 2% each). Rugae numbers (total, primary, secondary, fragmentary) were symmetrical but shape, direction and the occurrence of convergence were asymmetrical (p < 0.05). None of the examined characteristics showed gender dimorphism. Tabulated comparisons disclosed the equality of rugae patterns as major differences with findings from other Mediterranean studies. CONCLUSIONS: The palatal rugae in the Lebanese population display shape distinct from other reported Mediterranean and non-Caucasian populations. Studies in large samples and primary comparisons with other Mediterranean populations are warranted.

Association among geometric configurations of palatal rugae.

BACKGROUND: The associations between the length and morphological shape-related characteristics of palatal rugae have not been fully explored. OBJECTIVE: We aimed to assess the possible association among various geometric configurations of the palatal rugae in an adult population. MATERIALS AND METHODS: The maxillary dental casts of 217 non-growing subjects (95 males, 122 females, mean age 25.5±7.6 years) were scanned (laser scanning system Perceptron ScanWorks® V5) and digitized for linear measurements. The casts were also surveyed for visual categorization into curved, wavy, straight and other topographical forms, along with spatial direction of the rugae and the presence of unification. The rugae were categorized as primary, secondary, and fragmentary based on their lengths (> 5mm, 2-3mm, < 2mm, respectively). Chi square and one-way ANOVA and post-hoc tests were used to compare the palatal rugae groupings. RESULTS: Primary and backward-directed rugae prevailed in the total sample (84.7% and 49.3%, respectively). Wavy form was dominant among primary lengths, while straight form was associated with the shorter secondary and fragmentary groups (p=0.0042). Absence of unification was the norm (88.8%). CONCLUSIONS: Associations of length and shape characteristics among palatal rugae combine wavy patterns with increased length, and straight forms with shorter folds. These features contribute to the definition of ruga individuality in combination rather than separately.

Risk factors for nonpurulent leg cellulitis: a systematic review and meta-analysis.

Nonpurulent cellulitis is an acute bacterial infection of the dermal and subdermal tissues that is not associated with purulent drainage, discharge or abscess. The objectives of this systematic review and meta-analysis were to identify and appraise all controlled observational studies that have examined risk factors for the development of nonpurulent cellulitis of the leg (NPLC). A systematic literature search of electronic databases and grey literature sources was performed in July 2015. The Newcastle-Ottawa Scale (NOS) was used to assess methodological quality of included studies. Of 3059 potentially eligible studies retrieved and screened, six case-control studies were included. An increased risk of developing NPLC was associated with previous cellulitis [odds ratio (OR) 40·3, 95% confidence interval (CI) 22·6-72·0], wound (OR 19·1, 95% CI 9·1-40·0), current leg ulcers (OR 13·7, 95% CI 7·9-23·6), lymphoedema/chronic leg oedema (OR 6·8, 95% CI 3·5-13·3), excoriating skin diseases (OR 4·4, 95% CI 2·7-7·1), tinea pedis (OR 3·2, 95% CI 1·9-5·3) and body mass index > 30 kg m-2 (OR 2·4, 95% CI 1·4-4·0). Diabetes, smoking and alcohol consumption were not associated with NPLC. Although diabetics may have been underrepresented in the included studies, local risk factors appear to play a more significant role in the development of NPLC than do systemic risk factors. Clinicians should consider the treatment of modifiable risk factors including leg oedema, wounds, ulcers, areas of skin breakdown and toe-web intertrigo while administering antibiotic treatment for NPLC.

Resolving Fine-Scale Heterogeneity of Co-seismic Slip and the Relation to Fault Structure.

Fault slip distributions provide important insight into the earthquake process. We analyze high-resolution along-strike co-seismic slip profiles of the 1992 Mw = 7.3 Landers and 1999 Mw = 7.1 Hector Mine earthquakes, finding a spatial correlation between fluctuations of the slip distribution and geometrical fault structure. Using a spectral analysis, we demonstrate that the observed variation of co-seismic slip is neither random nor artificial, but self-affine fractal and rougher for Landers. We show that the wavelength and amplitude of slip variability correlates to the spatial distribution of fault geometrical complexity, explaining why Hector Mine has a smoother slip distribution as it occurred on a geometrically simpler fault system. We propose as a physical explanation that fault complexity induces a heterogeneous stress state that in turn controls co-seismic slip. Our observations detail the fundamental relationship between fault structure and earthquake rupture behavior, allowing for modeling of realistic slip profiles for use in seismic hazard assessment and paleoseismology studies.

Threshold for sand mobility on Mars calibrated from seasonal variations of sand flux.

Coupling between surface winds and saltation is a fundamental factor governing geological activity and climate on Mars. Saltation of sand is crucial for both erosion of the surface and dust lifting into the atmosphere. Wind tunnel experiments along with measurements from surface meteorology stations and modelling of wind speeds suggest that winds should only rarely move sand on Mars. However, evidence for currently active dune migration has recently accumulated. Crucially, the frequency of sand-moving events and the implied threshold wind stresses for saltation have remained unknown. Here we present detailed measurements of Nili Patera dune field based on High Resolution Imaging Science Experiment images, demonstrating that sand motion occurs daily throughout much of the year and that the resulting sand flux is strongly seasonal. Analysis of the seasonal sand flux variation suggests an effective threshold for sand motion for application to large-scale model wind fields (1-100 km scale) of τ(s)=0.01±0.0015 N m(-2).

Safety and efficacy of a novel nasal spray for maxillary dental anesthesia.

This study examines the efficacy, safety, and tolerability of a nasal spray to induce anesthesia of maxillary teeth. Forty-five healthy adults requiring restoration of one maxillary tooth were randomized in a 1:2 ratio to receive (1) an intra-oral lidocaine-epinephrine injection with buffered saline nasal spray bilaterally, or (2) a tetracaine hydrochloride-oxymetazoline hydrochloride nasal spray bilaterally with sham injection. Primary endpoints were use of rescue anesthesia and patient global pain assessment. Secondary outcomes included vital sign changes, soft-tissue anesthesia, and treatment-emergent adverse events. In intent-to-treat analysis, 25 of 30 patients given nasal spray (83.3%) did not require rescue anesthesia. Proportion of anesthesia successes for nasal spray was significantly different from the hypothesized placebo anesthesia success of 30% (one-sided p value < .0001 by exact binomial test). Mean duration of soft-tissue anesthesia did not differ significantly by treatment for 3 of 4 sites assessed. No serious adverse events or systemic effects were observed. Tetracaine hydrochloride-oxymetazoline nasal spray appears to provide adequate and safe anesthesia for the majority of maxillary dental procedures. Based on the results from this Phase 2 study, pivotal trials are warranted to validate these findings in an expanded patient population.

Earth-like sand fluxes on Mars.

Strong and sustained winds on Mars have been considered rare, on the basis of surface meteorology measurements and global circulation models, raising the question of whether the abundant dunes and evidence for wind erosion seen on the planet are a current process. Recent studies showed sand activity, but could not determine whether entire dunes were moving--implying large sand fluxes--or whether more localized and surficial changes had occurred. Here we present measurements of the migration rate of sand ripples and dune lee fronts at the Nili Patera dune field. We show that the dunes are near steady state, with their entire volumes composed of mobile sand. The dunes have unexpectedly high sand fluxes, similar, for example, to those in Victoria Valley, Antarctica, implying that rates of landscape modification on Mars and Earth are similar.

Heart transplantation in 107 cases of Chagas' disease.

INTRODUCTION: Chagas' disease is endemic in South America. OBJECTIVE: This research reviewed the experience with cardiac transplantation in Chagas' disease, emphasizing reactivation, immunosuppression, and mortality. METHODS: Over 25 years from March 1985 to March 2010, 107/409 (26.2%) patients with Chagas' disease underwent heart transplantation, patients including 74 (71.1%) men and 72 (67.2%), in functional class IV with 33 (30.8%) on vasopressors and 17 (10.7%) on mechanical circulatory support. RESULTS: The diagnosis of disease reactivation was performed by identifying the parasite in the myocardium (n = 23; 71.8%) in the subcutaneous tissue (n = 8; 25.0%), in blood (n = 11; 34.3%), or in central nervous tissue (n = 1; 3.1%). Hospital mortality was 17.7% (n = 19) due to infection (n = 6; 31.5%), graft dysfunction (n = 6; 31.5%), rejection (n = 4; 21.1%), or sudden death (n = 2; 10.5%). Late mortality was 27 (25.2%) cases, which were distributed as: rejection (n = 6; 22.2%), infection (n = 6; 22.2%), (n = lymphoma 4; 14.8%), sarcoma (n = 2; 7.4%), for constrictive pericarditis (n = 2; 7.4%) reactivation of Chagas' disease in the central nervous system (n = 1; 7.1%). CONCLUSIONS: Transplantation in Chagas' disease has peculiar problems that differ from other etiologies due to the possibility of disease reactivation and the increased possibility of emergence of cancers. However, transplantation is the only treatment able to modify the natural progression of the disease in its terminal phase. Early diagnosis and rapid introduction of benzonidazole reverses the histological patterns. Immunosuppression, especially steroids, predisposes to the development of cancer and disease reactivation.

Early detection of Aspergillus carbonarius and A. niger on table grapes: a tool for quality improvement.

Aspergillus carbonarius and A. niger aggregate are the main fungal contaminants of table grapes. Besides their ability to cause black rot, they can produce ochratoxin A (OTA), a mycotoxin that has attracted increasing attention worldwide. The objective of this work was to set up a simple and rapid molecular method for the early detection of both fungi in table grapes before fungal development becomes evident. Polymerase chain reaction (PCR)-based assays were developed by designing species-specific primers based on the polyketide synthases (PKS(S)) sequences of A. carbonarius and A. niger that have recently been demonstrated to be involved in OTA biosynthesis. Three table grape varieties (Red globe, Crimson seedless, and Italia) were inoculated with A. carbonarius and A. niger aggregate strains producing OTA. The extracted DNA from control (non-inoculated) and inoculated grapes was amplified by PCR using ACPKS2F-ACPKS2R for A. carbonarius and ANPKS5-ANPKS6 for A. niger aggregate. Both primers allowed a clear detection, even in symptomless samples. PCR-based methods are considered to be a good alternative to traditional diagnostic means for the early detection of fungi in complex matrix for their high specificity and sensitivity. The results obtained could be useful for the definition of a 'quality label' for tested grapes to improve the safety measures taken to guarantee the production of fresh table grapes.

Applicability of the dimodent equation of sex prediction in a Lebanese population sample.

BACKGROUND: Sexual dimorphism represents a group of morphologic characteristics that differentiate a male from a female. Among these dimorphic traits, tooth size has been evaluated in various populations for its interest in anthropologic and forensic applications. Recent studies have shown that dental dimorphism is population-specific and that the most dimorphic tooth is the mandibular canine. In addition to the dimension of single teeth in dimorphic dental assessment, dimorphism has been evaluated, using equation of prediction, applying various dimensions of one or more teeth or indices. PURPOSE: The objective of this preliminary study was to evaluate the applicability of the Dimodent predictive equation in sex determination in a sample of Lebanese young individuals. MATERIALS AND METHODS: Mesiodistal widths of the mandibular canine and lateral incisor were measured from dental casts of the permanent teeth of 60 Lebanese University dental students (30 males and 30 females), aged 18-25 years. The sex-predictive equation of Fronty was applied to calculate the percentage of accurately-diagnosed sexes. RESULTS: Accuracy of sex prediction ranged from 63.3% for males and 90% for females. Overall, the Dimodent equation enabled a correct sex determination in 76.7% of the cases. When compared to the accuracy obtained with this equation in a French population sample, the accuracy was significantly different (Z=3.1225). CONCLUSIONS: This research supports earlier studies that sexual dimorphism is population specific. The difficulty or lack of dimorphism seems to originate from male subjects. Further investigations should include the preparation of population-specific prediction tables and testing their accuracy in a larger sample with a strongly-established Lebanese background.

A study of the interactions of an immunoglobulin light chain with artificial and B-lymphocyte membranes.

The binding of an immunoglobulin lambda light chain (IgLC) to synthetic and biological membranes was monitored in real-time using a recently developed, time-resolved fluorescence technique. Lambda IgLC purified from the urine of patients with multiple myeloma, were used in studies of protein-membrane interactions. The association of the lambda IgLC dimer with B-lymphocytes was shown to be stabilised predominantly by non-polar interactions. Furthermore, it was found that following binding to synthetic phospholipid membranes, a reorientation of the light chain occurred which resulted in a change in the distribution of charged residues at the lipid-water interface. The rate constants associated with the binding event were calculated, and appear to comprise both temperature insensitive and sensitive components. The calculated activation energies of the binding and reorientation events were found to be 13.53 KJmol(-1) and 87.89 KJmol(-1), respectively. The large activation energy associated with the reorientation phase suggests the movement of large protein domains, possibly involving a whole immunoglobulin domain. The binding and reorganisation of the IgLC upon the phospholipid membrane may confer novel biological functions to the bound protein and potentially contribute to such phenomenon as myeloma-associated immuno-suppression.

Interactions of macromolecules with the mammalian cell surface.

The characterisation of fluoresceinphosphatidylethanolamine (FPE) as a real-time indicator of the electrostatic nature of the cell membrane surface is described. The conditions appropriate for the labelling of cell membranes and the implementation of FPE as a tool to monitor the interactions of various proteins and peptides with membranes are outlined. Some complications attributed to the erythrocyte glycocalyx are examined. In addition it is shown using neuraminidase as an example, that some types of enzyme-catalysed reactions on the cell surface may be monitored in real time. It is also shown that information concerning the binding of several proteins such as serum albumin and monoclonal antibodies are accessible with this technique. The albumin in particular is shown to exhibit a saturation of binding, the analysis of which indicates that the dissociation constant for erythrocytes was determined to be 8 microM and for lymphocytes to be almost 3 microM. On the basis of this comparison together with artificial membranes, the membrane protein components of the lymphocyte surface are implicated in the binding of albumin or the erythrocyte membrane proteins reduce the affinity of the cell surface for albumin.

Inhibition of proliferation of human leukaemia 60 cells by methylglyoxal in vitro.

Methylglyoxal (2-oxopropanal) is the physiological substrate of the glyoxalase system. When exogenous methylglyoxal (50 microM-1 mM) was added to human leukaemia 60 (HL60) cells in culture (5 x 10(4) cells/ml), inhibition of growth and toxicity was induced. The median growth inhibitory concentration IC50 value was 238 +/- 2 microM. There was little differentiation of HL60 cells induced by methylglyoxal (a maximum of 2% differentiation with 500 microM methylglyoxal). There was no similar toxicity induced by methylglyoxal in corresponding differentiated cells, neutrophils, under the same culture conditions. Cell growth and toxicity induced by methylglyoxal (250 microM) in HL60 cells occurred in the initial 24 h of culture, after which residual surviving cells exhibited normal growth kinetics. It could also be prevented by replacing the culture medium in the initial 6 h of culture; thereafter, irreversible toxicity developed, reaching the maximum value after 24 h of culture. Growth arrest and toxicity induced by methylglyoxal increased with increasing serum composition of the medium. The mechanism of toxicity is unknown.