Use of a gamma-2 herpesvirus as a vector to deliver antibodies to rhesus monkeys.

The gamma-2 herpesvirus of rhesus monkeys, rhesus monkey rhadinovirus (RRV), persists principally in B cells of its host. We constructed recombinant strains of RRV expressing the rhesus monkey-derived anti-SIV monoclonal antibodies 4L6 and 5L7 and compared the RRV-mediated in vivo delivery of these antibodies in rhesus monkeys with previous studies that utilized intramuscular delivery with an adeno-associated virus (AAV) vector. Recombinant RRV-4L6 and RRV-5L7 were both shown to stably produce the antibodies in persistently infected B-cell lines in culture. Two RRV-negative rhesus monkeys were experimentally infected with recombinant RRV-4L6 and two with recombinant RRV-5L7. Following infection, the appearance of the delivered antibody was readily detected in all four animals. However, the levels of the delivered antibody were considerably lower than what has been typically observed following intramuscular AAV delivery. Furthermore, three of the four monkeys had an antibody response to the delivered antibody as had been observed previously with intramuscular AAV delivery of these same antibodies. We conclude that this recombinant herpesvirus has no inherent advantage over AAV for delivery of potentially therapeutic monoclonal antibodies in a rhesus monkey model.

Inexplicable Outcome of Early Appearance of Hepatocellular Carcinoma in the Allograft After Deceased Donor Liver Transplantation: A Case Report.

BACKGROUND: This case represents the earliest appearance of de novo HCC after liver transplantation (OLT) compared with cases of previously reported literatures. CASE REPORT: A 45-year-old man underwent deceased donor OLT owing to decompensated liver cirrhosis. He had YMDD viral mutation and hepatitis B (HBV) and C (HCV) coinfection but no tumor was found in the liver on MRI before OLT. The donor was a healthy young female donor who was HCV and HBV negative. There was no tumor in the explant liver. After OLT, HCV RNA and hepatitis B surface antigen became undetectable with DNA-positive HBV. Nine months after OLT, a computed tomography (CT) scan was performed owing to abdominal pain, detecting a mass occupying the right lobe that depicted enhanced characteristics typical of HCC. The chest CT demonstrated metastatic lung nodules in the right basal lower lobe. Fluorescence in situ hybridization showed tumor cells from the recipient. CONCLUSIONS: To the best of our knowledge, this is the first report of de novo hepatocellular carcinoma that has emerged within a short period of undergoing OLT.

Semiconducting-to-metallic photoconductivity crossover and temperature-dependent Drude weight in graphene.

We investigate the transient photoconductivity of graphene at various gate-tuned carrier densities by optical-pump terahertz-probe spectroscopy. We demonstrate that graphene exhibits semiconducting positive photoconductivity near zero carrier density, which crosses over to metallic negative photoconductivity at high carrier density. These observations can be accounted for by the interplay between photoinduced changes of both the Drude weight and carrier scattering rate. Our findings provide a complete picture to explain the opposite photoconductivity behavior reported in (undoped) graphene grown epitaxially and (doped) graphene grown by chemical vapor deposition. Notably, we observe nonmonotonic fluence dependence of the photoconductivity at low carrier density. This behavior reveals the nonmonotonic temperature dependence of the Drude weight in graphene, a unique property of two-dimensional massless Dirac fermions.

Perfusion defects detected after liver transplantation on multidetector computerized tomography: short- and long-term follow-up.

BACKGROUND: Perfusion defects are sometimes found during the follow-up computerized tomography (CT) after liver transplantation (OLT). This study sought to determine the short- and long-term outcomes of perfusion defects observed after OLT with the use of multidetector CT. METHODS: From February 4, 2004, to December 8, 2011, a total 46 LTs were performed in our hospital owing to end-stage liver cirrhosis (n = 43), liver cirrhosis with hepatocellular carcinoma (HCC; n = 1), combined HCC with cholangiocellular carcinoma (CCC; n = 1), or hepatic failure from acute hepatitis A (n = 1). The transplanted livers were procured from cadaveric (n = 24) or living related donors (n = 22). The average age of the recipient was 53.3 ± 10.4 years. The male-female ratio was 30:16. Postoperative multidetector CT was performed with a dynamic sequence in 203 examinations and with a portal phase in 46 examinations. The contrast media was Radisense. The rate of injection of 120 mL was 3 mL/s with a power injector; the iodine concentration was 300 or 370 mg/dL. Follow-up ranged from 3 months 3 days to 7 years 363 days. We classified perfusion defects as chronic segmental or subsegmental benign ischemia, transient focal perfusion defects, benign subcapsular ischemia, or fatal whole liver perfusion defects. RESULTS: There were 3 cases of chronic segmental or subsegmental benign ischemia, 8 focal transient perfusion defects, 1 benign subcapsular ischemia, and 4 fatal whole liver perfusion defects. Except the fatal cases, all other perfusion defects occurred in the courses of benign conditions without resection or reoperation. CONCLUSIONS: Most perfusion defects were benign and uneventful, requiring no treatment, with the exception of fatal whole liver perfusion defects, which resulted in death after detection.

Cryoprotection of fibroblasts by carboxylated poly-L-lysine upon repeated freeze/thaw cycles.

The cryoprotection of carboxylated h-poly-L-lysine (COOH-PLL) was investigated on fibroblasts [L-929 cells and human dermal fibroblasts (HDFs)] during multiple freeze/thaw cycles. COOH-PLL was not toxic to two fibroblast cell types even at 25% (w/v) concentration, whereas dimethylsulphoxide (DMSO) was highly toxic over 3.13% (v/v). When L-929 cells were subjected to 5 freeze/thaw cycles, the media containing 7.5% (w/v) COOH-PLL maintained cell morphology and significantly suppressed growth inhibition as well as cell detachment (P < 0.05). The result was comparable to the media containing 10% (v/v) DMSO. For HDFs, COOH-PLL could effectively retain cell viability and proliferation against 3 freeze/thaw cycles. Cell viability of HDFs was decreased after 5 freeze/thaw cycles, but COOH-PLL exerted better cryoprotection. The cell type might account for the difference in the observations. The data demonstrated that COOH-PLL is a good cryoprotectant for mammalian cells against repeated freeze/thaw cycles, and may be used for cell preservation in fields of cell transplantation, tissue engineering and regenerative medicine.

Preoperative determination of anatomic variations of the small saphenous vein for varicose vein surgery by three-dimensional computed tomography venography.

OBJECTIVE: To define the anatomical variations of small saphenous vein (SSV) for varicose vein (VV) surgery by three-dimensional computed tomography venography (3D-CTV) and to analyse the impact of this preoperative evaluation on surgical outcomes. METHODS: A total of 120 consecutive limbs with SSV insufficiency having undergone VV surgery from January 2005 until December 2007 were enrolled. The medical records and images were analysed retrospectively. RESULTS: The relationship between SSV and gastrocnemial vein (GNV) were categorized into two: (a) SSV and GNV drained to popliteal vein (PV) separately (100 limbs, 87%) and (b) SSV and GNV made common channel which drained to PV (15 limbs, 13%). Saphenopopliteal junction morphology was normal (75 limbs), severe tortuosity near PV (19 limbs), ampullary ectasia (4 limbs) and duplicated drainage to PV (2 limbs). No recurrence of VV was noted. CONCLUSIONS: CTV can provide thorough preoperative anatomic information of the SSV variations and reduce the recurrence of VV.

Green tea consumption, abdominal obesity as related factors of lacunar infarction in Korean women.

OBJECTIVES: Our purpose was to evaluate interaction of green tea consumption and abdominal obesity as related factors for lacunar infarction in Korean women. DESIGN: A hospital-based, incident case-control study. SETTINGS: The Prevention and Managements of Stroke in Women study. PARTICIPANTS: Cases (n=233) of first incident lacunar infarction were enrolled and matched by age to stroke-free hospital controls (n=204). MEASUREMENTS: The data were collected through face-to-face interviews by well trained research assistants to assess demographic, medical, lifestyle, marital status, religions status, green tea consumptions, family history of stroke, smoking status, alcohol consumption, meat and vegetable intake frequency, and past history of hypertension. Biochemical analysis, fasting blood specimens for lipid, glucose, and cholesterol level were acquired. RESULTS: Compared with the non green tea consumer and obese women group, only the green tea consumption and non obese women group had a protective effect of lacunar infarction when adjusted for age, and age plus diet factors (OR, 0.23; 95% CI, 0.09, 0.59; OR, 0.21; 95% CI, 0.08, 0.56 respectively), but lost their significance after adjustment for age, diet factors, vascular risk factors and full model included atherogenic index factors (OR, 0.32; 95% CI, 0.09 to 1.01; OR, 0.49; 95% CI, 0.12, 1.89 respectively). CONCLUSIONS: The interaction of green tea consumption and non obesity have reduced risk of lacunar infarction, but not after adjustment for age, diet factors, vascular risk factors and atherogenic index. Also individually green tea consumption and abdominal obesity have failed to find an independent relationship with lacunar infarction after adjustment by all risk factors. Green tea consumption and green tea consumption with non obese group seemed to have a protective effect for lacunar infarction. In the results of our study, these results still remain controversial, and then we need further and larger study to get at the root of real causal effect of both relationships.

Beneficial effects of Undaria pinnatifida ethanol extract on diet-induced-insulin resistance in C57BL/6J mice.

This study was performed to evaluate the beneficial effect of Undaria pinnatifida ethanol extract (UEFx) on insulin resistance in diet-induced obese mice. A high-fat diet was supplemented with the UEFx at 0.69% (wt/wt) dose, which contains an equivalent amount of 0.02% fucoxanthin (wt/wt), or with Fx at 0.02% (wt/wt) dose in diet. After 9 weeks, both UEFx supplement significantly lowered the amount of visceral fat, the size of adipocyte, the fasting blood glucose concentration, the plasma insulin and the insulin resistance index similar to pure as shown by Fx supplement, compared to the high-fat (HF) control group. Blood glucose level was negatively correlated with hepatic glucokinase activity (r = -0.533, p < 0.05), whereas positively correlated with hepatic gluconeogenic enzyme activities (r = 0.463, p < 0.05 for glucose-6-phosphatase; r = 0.457, p < 0.05 for phosphoenolpyruvate carboxykinase). Ratio of hepatic glucokinase/glucose-6-phosphatase and glycogen content were significantly elevated by the UEFx and Fx supplements. Supplementation of the UEFx as well as Fx seemed to stimulate the ß-oxidation activity and inhibit the phosphatidate phosphohydrolase activity resulting in a decrease in the hepatic lipid droplet accumulation. The results indicate that the UEFx can prevent insulin resistance and hepatic fat accumulation that is partly mediated by modulating the hepatic glucose and lipid homeostasis in the high fat-induced obese mice.

Modeling and experimental verification of plasmas induced by high-power nanosecond laser-aluminum interactions in air.

It has been generally believed in literature that in nanosecond laser ablation, the condensed substrate phase contributes mass to the plasma plume through surface evaporation across the sharp interface between the condensed phase and the vapor or plasma phase. However, this will not be true when laser intensity is sufficiently high. In this case, the target temperature can be greater than the critical temperature, so that the sharp interface between the condensed and gaseous phases disappears and is smeared into a macroscopic transition layer. The substrate should contribute mass to the plasma region mainly through hydrodynamic expansion instead of surface evaporation. Based on this physical mechanism, a numerical model has been developed by solving the one-dimensional hydrodynamic equations over the entire physical domain supplemented by wide-range equations of state. It has been found that model predictions have good agreements with experimental measurement for plasma front location, temperature, and electron number density. This has provided further evidence (at least in the indirect sense), besides the above theoretical analysis, that for nanosecond laser metal ablation in air at sufficiently high intensity, the dominant physical mechanism for mass transfer from the condensed phase to the plasma plume is hydrodynamic expansion instead of surface evaporation. The developed and verified numerical model provides useful means for the investigation of nanosecond laser-induced plasma at high intensities.

Distribution and determinants of maximal physical work capacity of Korean male metal workers.

The distribution of maximal physical work capacity (MPWC) can be used to establish an upper limit for energy expenditure during work (EEwork). If physically demanding work has wearing effects, there will be a negative relationship between MPWC and workload. This study was conducted to investigate the distribution of MPWC among Korean metal workers and to examine the relationship between workload and MPWC. MPWC was estimated with a bicycle ergometer using a submaximal test. Energy expenditure was estimated by measuring heart rates during work. The study subjects were 507 male employees from several metal industries in Korea. They had a lower absolute VO2max than the Caucasian populations described in previous studies. The older workers had a lower physical capacity and a greater overload at work. A negative relationship was found between MPWC and workload across all age groups. Upper limits for EEwork for all age groups and for older age groups are recommended based on the 5th percentile value of MPWC.

Chromosome aberration and lipid peroxidation in chromium-exposed workers.

Chromosome aberration frequency and lipid peroxidation levels were analyzed to investigate their efficacy as biological markers for monitoring the genotoxicity and oxidative damage in Korean chromium (Cr)-exposed workers. Fifty-one Cr-exposed workers and 31 age-matched controls in ten chrome-plating plants were sampled. The Cr level was measured in the workers' blood and urine, and in the ambient air at the workplaces. The conventional Giemsa staining method and fluorescence in situ hybridization (FISH) technique were used for chromosome aberration analysis. Spectrum green whole chromosome paint specific for chromosome 4 was used in the FISH procedure. As for lipid peroxidation, malondialdehyde (MDA) was measured in the blood plasma as thiobarbituric acid-reactive substances (TBARS). The blood Cr concentration was statistically correlated with both the frequency of chromatid exchange and the total frequency of chromosome/chromatid breaks and exchanges, as detected by the Giemsa staining. Meanwhile, the frequency of translocation, as detected by the FISH technique, was significantly higher in the Cr-exposed workers than in the controls and it correlated with the blood Cr concentration. Although the concentration of MDA, the metabolite of lipid peroxidation, in the exposed workers was higher than that of the controls, no statistically significant correlation between the MDA level and the blood or urine Cr levels was observed. Accordingly, the genotoxicity and oxidative damage (plasma lipid peroxidation) in the Korean Cr-exposed workers were consequential at quite low exposure levels, plus chromosome rearrangement, especially translocation, was clearly evident as a biological response marker for Cr exposure based on a significant positive correlation between the translocations detected by FISH and the Cr in the blood.

Comparison of myocardial infarction with sequential ligation of the left anterior descending artery and its diagonal branch in dogs and sheep.

We report a comparison of the effects of myocardial infarction in dogs and sheep using sequential ligation of the left anterior descending artery (LAD) and its diagonal branch (DA), with hemodynamic, ultrasonographic and pathological evaluations. Five animals were used in each group. After surgical preparation, the LAD was ligated at a point approximately 40% of the distance from the apex to the base of the heart, and after one hour, the DA was ligated at the same level. Hemodynamic and ultrasonographic measurements were performed preligation, 30 minutes after LAD ligation, and 1 hour after DA ligation. As a control, two animals in each group were used for the simultaneous ligation of the LAD and the DA. Two months after the coronary ligation, the animals were evaluated as previously, and killed for postmortem examination of their hearts. All seven animals in the dog group survived the experimental procedures, while in the sheep group only animals with sequential ligation of the LAD and DA survived. Statistically significant decreases in systemic arterial blood pressure and cardiac output, and an increase in the pulmonary artery capillary wedge pressure (PACWP) were observed one hour after sequential ligation of the LAD and its DA in the sheep, while only systemic arterial pressures decreased in the dog. Ultrasonographic analyses demonstrated variable degrees of anteroseptal dyskinesia and akinesia in all sheep, but in no dogs. Data two months after coronary artery ligation showed significant increases in central venous pressure, pulmonary artery pressure, and PACWP in the sheep, but not in the dog. Left ventricular end-diastolic dimension and left ventricular end-systolic dimension in ultrasonographic studies were also increased only in the sheep. Pathologically, the well-demarcated thin-walled transmural anteroseptal infarcts with chamber enlargement were clearly seen in all specimens of sheep, and only-mild-to-moderate chamber enlargements with endocardial fibrosis were observed in the dog hearts. In conclusion, this study confirms that the dog is not a suitable model for myocardial infarction with failure by coronary artery ligation despite negligent operative mortality, when compared directly with an ovine model.

Double-blind naltrexone and placebo comparison study in the treatment of pathological gambling.

BACKGROUND: The authors' goal was to assess the efficacy and tolerability of naltrexone in the treatment of pathologic gambling disorder. METHODS: Eighty-three subjects who met criteria for DSM-IV pathologic gambling disorder were enrolled in a 1-week single-blind placebo lead-in followed by an 11-week double-blind naltrexone or placebo trial. Naltrexone was started at 25 mg/day and titrated upward until maximum symptom improvement or 250 mg/day was achieved. Gambling symptom change was assessed with the patient-rated Clinical Global Impression (PG-CGI-PT), clinician-rated CGI (PG-CGI-MD), and the Gambling Symptom Rating Scale (G-SAS). Side effects were monitored weekly and liver function tests biweekly. RESULTS: Data from 45 patients were analyzed. Using random regression analysis, significant improvement was noted in all three gambling symptom measures: patient-rated Clinical Global Impression, p <.001; clinician-rated CGI, p <.001; Gambling Symptom Rating Scale, p <.019. At study end, 75% of subjects taking naltrexone were much or very much improved on both the PE-CEI PT and the PG-CGI-MD, compared with only 24% of those on placebo. Elevated liver enzymes occurred in four subjects who were taking analgesics concurrently. Nausea was common during the first week of treatment. CONCLUSIONS: Results suggest that naltrexone is effective in reducing the symptoms of pathologic gambling. Until further studies corroborate the present findings, our report should be interpreted cautiously.

Variable numbers of TTC repeats in Mycobacterium leprae DNA from leprosy patients and use in strain differentiation.

Strain differentiation of Mycobacterium leprae would be of great value for epidemiological investigation to identify the infectious sources of leprosy, to understand transmission patterns, and to distinguish between relapse and reinfection. From the M. leprae genome sequence database, TTC DNA repeats were identified. Primer sets designed to amplify the region flanking TTC repeats revealed PCR products of different sizes, indicating that the number of repeats at each locus may be variable among M. leprae strains. The TTC repeats were not found in Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium marinum, or human tissues, which indicated their specificity to M. leprae. Sequence analysis of the TTC repeat region in each of the M. leprae strains showed a variation of 10 to 37 repeats. In the M. leprae strains of 34 multibacillary patients at Cebu, Philippines, M. leprae with 24 and 25 TTC repeats was most common, and this was followed by strains with 14, 15, 20, 21, and 28 repeats. This study thus indicates that there are variable numbers of TTC repeats in a noncoding region of M. leprae strains and that the TTC region may be useful for strain differentiation for epidemiological investigations of leprosy.

Reduction of hexavalent chromium collected on PVC filters.

Chromium exists at various valences, including elemental, trivalent, and hexavalent chromium, and undergoes reduction-oxidation reactions in the environment. Since hexavalent chromium is known as a human carcinogen, it is most important to evaluate the oxidation-reduction characteristics of the hexavalent chromium species. Although hexavalent chromium can be reduced to trivalent state, the detailed information on this in workplace environments is limited. The purpose of this study was to investigate hexavalent chromium reduction in time in various conditions. A pilot chrome plating operation was prepared and operated in a laboratory for this study. There was evidence that the hexavalent chromium was reduced by time after mist generation. The percentage ratio (with 95% confidence intervals in parentheses) of hexavalent chromium to total chromium was almost 100% (99.1 approximately 102.3) immediately after mist generation, and was reduced to 87.4% (84.8 approximately 89.9) at 1 hour and 81.0% (78.3 approximately 83.5) at 2 hours, respectively. Another test indicated that hexavalent chromium collected on PVC filters was also reduced by time after sampling. Hexavalent chromium was reduced to 90.8% (88.2 approximately 93.3) at 2 hours after sampling. It also was found that hexavalent chromium was reduced during storage in air. It is recommended that air samples of hexavalent chromium be protected against reduction during storage.

The in vitro blood compatibility of poly(ethylene oxide)-grafted polyurethane/polystyrene interpenetrating polymer networks.

Poly(ethylene oxide) (PEO)-grafted polyurethane (PU)/polystyrene (PS) interpenetrating polymer networks (IPNs) were synthesized. The effects of the mobile pendant PEO chains with their microphase separated structure on blood-compatibility were investigated. The morphology of both the fracture surface as well as the top surface indicate that the size of the dispersed domains of the PS-rich phase decreased as the grafting with the PEO was increased. The swelling ratio also decreased as the grafting with the PEO was increased. However, the dynamic contact angle and the interfacial energy between IPN surface and water decreased, due to the structural reorganization of the pendant PEO chains. PU/PS IPNs have an excellent mechanical property as compared with PU homopolymers. The adsorption of bovine plasma fibrinogen (BPF) onto the PU/PS IPNs and PU homopolymers was effectively suppressed by the PEO-grafting. In the platelet adhesion test, the amount of platelets adsorbed, activated, and/or coagulated upon the PEO-grafted PU/PS IPNs were reduced when compared to the ungrafted PU homopolymers.

Biochemical, molecular and physiological characterization of a new beta-casein variant detected in Korean cattle.

There are seven known genetic variants of bovine beta-casein (beta-CN)--A1, A2, A3, B, C, D and E. In this study, we identified a new genetic variant (named beta-CN H) which migrates slower than the other variants in acidic starch gel electrophoresis. We confirmed through protein and DNA sequence analyses that the H variant differs at five residues from the A2 sequence: Arg25/Cys, Leu88/Ile, Gln117/Glu, Glu175/Gln and Gln195/Glu. Of these substitutions the 25th residue was contained in the casein phosphopeptide (CPP) region. In rats, calcium solubilizing effect of the CPP of bovine variant H was increased by approximately 23% compared with that of the CPP of non-H. Using extensive Korean Bos taurus pedigrees, we confirmed that beta-CN H was controlled by a codominant allele.

Idiopathic parkinsonism with superimposed manganese exposure: utility of positron emission tomography.

It is difficult to distinguish manganism from idiopathic parkinsonism by clinical signs only. Case history and examination: A 48-year-old welder for over 10 years complained of masked face, right side (arm and leg) resting tremor, and bradykinesia for over one year. Magnetic resonance imaging (MRI) findings showed symmetrical high signal intensities in the globus pallidus on T1 weighted image. These intensities disappeared almost completely six months after cessation of exposure. 18F-6-fluorodopa (18F-dopa) positron emission tomography (PET) findings showed reduced 18F-dopa uptake in the left putamen, findings which appear in idiopathic parkinsonism. A PET study is necessary to distinguish manganism from idiopathic parkinsonism, especially in a working environment with elevated Mn concentrations, such as welding.

Biological control of fusarium wilt of cucumber by chitinolytic bacteria.

ABSTRACT Two chitinolytic bacterial strains, Paenibacillus sp. 300 and Streptomyces sp. 385, suppressed Fusarium wilt of cucumber (Cucumis sativus) caused by Fusarium oxysporum f. sp. cucumerinum in nonsterile, soilless potting medium. A mixture of the two strains in a ratio of 1:1 or 4:1 gave significantly (P < 0.05) better control of the disease than each of the strains used individually or than mixtures in other ratios. Several formulations were tested, and a zeolite-based, chitosan-amended formulation (ZAC) provided the best protection against the disease. Dose-response studies indicated that the threshold dose of 6 g of formulation per kilogram of potting medium was required for significant (P < 0.001) suppression of the disease. This dose was optimum for maintaining high rhizosphere population densities of chitinolytic bacteria (log 8.1 to log 9.3 CFU/g dry weight of potting medium), which were required for the control of Fusarium wilt. The ZAC formulation was suppressive when added to pathogen-infested medium 15 days before planting cucumber seeds. The formulation also provided good control when stored for 6 months at room temperature or at 4 degrees C. Chitinase and beta-1,3-glucanase enzymes were produced when the strains were grown in the presence of colloidal chitin as the sole carbon source. Partial purification of the chitinases, followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and activity staining, revealed the presence of five bands with molecular masses of 65, 62, 59, 55, and 52 kDa in the case of Paenibacillus sp. 300; and three bands with molecular masses of 52, 38, and 33 kDa in the case of Streptomyces sp. 385. Incubation of cell walls of F. oxysporum f. sp. cucumerinum with partially purified enzyme fractions led to the release of N-acetyl-D-glucosamine (NAGA). NAGA content was considerably greater when pooled enzyme fractions (64 to 67) from Paenibacillus sp. were used, because they contained high beta-1,3-glucanase activity in addition to chitinase activity. Suppression of Fusarium wilt of cucumber by a combination of these two bacteria may involve the action of these hydrolytic enzymes.

Increase in signal intensities on T1-weighted magnetic resonance images in asymptomatic manganese-exposed workers.

OBJECTIVES: To clarify the clinical significance of increased signal intensities on T1 weighted magnetic resonance imaging (MRI) we performed a large-scale epidemiological study on asymptomatic manganese (Mn)-exposed workers with its focus on MRI. METHODS: We randomly selected 121 male workers out of a total of 750 workers including Mn-exposed, non-exposed manual, and non-exposed clerical workers in the factories. We studied environmental and biological monitoring, neurological examination, and MRI. RESULTS: The proportion of workers with increased signal intensities among the exposed, the non-exposed manual workers, and the non-exposed clerical workers was 46.1%, 18.8%, and 0%, respectively. Especially, 73.5% of the welders showed increased signal intensities. In no subject, were clinical signs of manganism observed. The pallidal index correlated with blood Mn concentration. CONCLUSION: Increase in signal intensities on the T1-weighted image reflect recent exposure to Mn, but not necessarily manganism. At which increase of signal intensity, the progression of manganism from Mn exposure occurs, remains to be solved.