Risk of malignancy in patients with psoriasis: a 15-year nationwide population-based prospective cohort study in Korea.

BACKGROUND: The association between psoriasis and risk of malignancy has not been thoroughly evaluated in a large longitudinal cohort of Asian population. OBJECTIVE: To determine the long-term risk of malignancy in Korean adult patients with psoriasis. METHODS: We conducted a nationwide population-based prospective cohort study with a 15-year observational period. During the baseline period (1997-2000), total 1 773 786 Korean subjects who received health insurance from the National Health Insurance System were enrolled and 5788 subjects were defined as a psoriasis group. The number of new-onset malignancy was collected during the observational period (2001-2015). RESULTS: Patients with psoriasis had a higher adjusted hazard ratio (aHR) for development of overall malignancy [aHR 1.08, 95% confidence interval (CI) 1.00-1.18] and gastric cancer (aHR 1.31, 95% CI 1.08-1.58) compared to controls. The risks of non-Hodgkin lymphoma and non-melanoma skin cancer were significantly increased only in patients with psoriasis who received systemic treatments (aHR 2.86, 95% CI 1.07-7.61 and aHR 3.93, 95% CI 1.47-10.47, respectively). CONCLUSION: Psoriasis is associated with long-term risk for overall malignancy in Koreans, which was primarily driven by the increased risk of gastric cancer.

Association of human adenovirus-36 in overweight Korean adults.

BACKGROUND: Although human adenovirus-36 (Ad-36) has been reported to be associated with obesity in US adults and children, Korean children and the Italian population, the association has not been found in Dutch or Belgian populations or in US military subjects. Therefore, we examined whether Ad-36 infection is associated with obesity in Korean adults. METHODS: A total of 540 age- and sex-matched individuals, who were normal weight, overweight or obese, were selected from participants in routine health examinations at the Ewha Womans University Medical Center. Overweight participants were defined as those with a body mass index (BMI) of 23 ≤ BMI<25 kg m(-2) and obese subjects were those with BMI ≥ 25 kg m(-2), according to the International Obesity Task Force definition. Ad-36 antibody was measured using a serum neutralization assay. RESULTS: Although more overweight participants than normal or obese subjects tested positive for the Ad-36 antibody (40%, 32.8% and 30%, respectively), the differences were not significant. The participants who tested positive for Ad-36 antibody had lower levels of triglycerides (TG) in each of the three groups, higher total cholesterol (TC) in the obese group and higher high-density lipoprotein-cholesterol (HDL-C) in both the normal and obese groups. The odds ratio (OR) for Ad-36 antibody positivity was greater in overweight than in normal subjects (OR=2.03; 95% confidence interval (CI), 1.16-3.55) after adjusting for age, sex and waist circumference. However, this OR was non-significant in the obese group (OR=1.56; 95% CI, 0.67-3.67). CONCLUSION: Ad-36 seems to be strongly associated with overweight, but not obese, Korean adults.

HLA polymorphism among Chinese patients with chronic plaque psoriasis: subgroup analysis.

BACKGROUND: HLA-Cw*06 has a strong influence on the clinical features and the susceptibility to psoriasis in different ethnicities. It is also used as a biomarker to predict the therapeutic efficacy of biologics, with inconsistent results. Additionally, most Asian patients with psoriasis do not carry HLA-Cw*06. OBJECTIVES: To determine additional HLA alleles which confer susceptibility or affect the severity of psoriasis in Chinese Han individuals. In addition, the potential of using HLA to predict treatment outcomes was also investigated. METHODS: We conducted a case-control association study in 199 Chinese patients with psoriasis and 200 unrelated healthy controls. HLA-B and HLA-C genotyping was performed and correlated with the therapeutic efficacy of the biologics, including alefacept, efalizumab, etanercept and ustekinumab. Patients with psoriasis were divided into group A (high-need patients with moderate to severe psoriasis) and B (general patients with psoriasis). RESULTS: The frequencies of HLA-B*60, HLA-B*75, HLA-Cw*06 and HLA-Cw*10 were significantly increased in patients with psoriasis compared with the healthy controls. However, the prevalence of HLA-Cw*06 was lower in group A compared with group B (6% vs. 17%, Pc=0·04). HLA-B*46 was found to be strongly associated with group A but not with group B patients with psoriasis. HLA-Cw*01/HLA-B*46 was also identified as a risk haplotype for Chinese patients with psoriasis, compatible with the results in Thais. Significant differences in response to biologics were observed between HLA-Cw*01+ and HLA-Cw*01- individuals in the alefacept treatment group, and between HLA-B*37+ and HLA-B*37-, and HLA-B*58+ and HLA-B*58- individuals in the efalizumab treatment group. CONCLUSIONS: In addition to HLA-Cw*06, the HLA-Cw*01/HLA-B*46 haplotype was also increased in Chinese patients with psoriasis. High-need patients with psoriasis had a lower frequency of HLA-Cw*06 but a higher prevalence of HLA-B*46 compared with general patients with psoriasis in our population.

SLURP1 mutation-impaired T-cell activation in a family with mal de Meleda.

BACKGROUND: Mal de Meleda (MDM) is palmoplantar erythrokeratoderma with an autosomal recessive inheritance and is caused by a mutation in the gene encoding SLURP-1 (lymphocyte antigen 6/urokinase-type plasminogen activator receptor related protein-1). SLURP-1 is an allosteric agonist to the nicotinic acetylcholine receptor (nAchR) and it regulates epidermal homeostasis. In addition, murine studies have shown that nAchR signalling is important for the regulation of T-cell function. Among the family members, patients with the homozygous SLURP1 (previously known as ARS component B) mutation are prone to melanoma and viral infection, which might link to defective T-cell function as well as a derangement of epidermal homeostasis. OBJECTIVES: To investigate the association of the SLURP1 gene mutation with T-cell activation in a Taiwanese family with MDM. To test that SLURP-1 is essential for T-cell activation. METHODS: Human peripheral blood mononuclear cells (PBMCs) were isolated from a Taiwanese MDM family bearing the G to A substitution in nucleotide 256 in the SLURP1 gene, corresponding to a glycine to arginine substitution at amino acid 86 (G86R) in the SLURP-1 protein. PBMCs from homozygotes and wild-type controls were stimulated with anti-CD3/anti-CD28 antibodies and the level of T-cell activation was determined by the stimulation index. RESULTS: PBMCs with the heterozygous and homozygous SLURP-1 G86R mutation had defective T-cell activation. This was restored by the addition of 0·5 µg mL(-1) recombinant human SLURP-1 protein. CONCLUSIONS: Patients with MDM with the homozygous SLURP-1 G86R mutation may have an impaired T-cell activation. The presence of wild-type SLURP-1 is essential for normal T-cell activation.

Narrowband ultraviolet B phototherapy for patients with refractory uraemic pruritus: a randomized controlled trial.

BACKGROUND: Pruritus is very common in uraemic patients, but the treatment remains challenging. Studies regarding narrowband ultraviolet B (NB-UVB) phototherapy for uraemic pruritus are rare. OBJECTIVES: To investigate whether or not NB-UVB phototherapy is an effective treatment for uraemic pruritus. METHODS: We conducted a single-blind, randomized, controlled trial for patients with refractory uraemic pruritus. The treatment group received NB-UVB phototherapy three times per week for 6 weeks. The dose of NB-UVB started from 210 mJ cm(-2) and was increased by 10% each time. The control group received time-matched exposures to long-wave UVA radiation. A visual analogue scale (VAS) score was evaluated weekly for pruritus intensity for 12 weeks. The characteristics of pruritus were also assessed by a questionnaire at baseline and after 6 weeks of phototherapy. RESULTS: Both the NB-UVB and control groups had significant and comparable improvement in the pruritus intensity VAS scores during the period of phototherapy and follow-up. Compared with the control group, the NB-UVB group showed a significant improvement in the involved body surface area affected by pruritus (P = 0·006), but not in sleep quality. More detailed regression and estimating analysis revealed that the patients in the NB-UVB group had lower pruritus intensity scores at week 6, week 10 and week 12. This may indicate a beneficial difference at certain time points, but the effect seems marginal. CONCLUSIONS: NB-UVB phototherapy does not show a significant effect in reducing pruritus intensity compared with a control group for refractory uraemic pruritus. Further studies are warranted.

Molecular characterization of dermatophytes of the Trichophyton mentagrophytes complex found in Taiwan with emphasis on their correlation with clinical observations.

BACKGROUND: Fungi of the Trichophyton mentagrophytes complex are important pathogenic dermatophytes capable of causing various human skin infections. There are many species and varieties involved in this complex. Due to morphological similarity and existing intermediate forms and variants, unequivocally separating these dermatophytes is not always straightforward, and sampling appropriate isolates for research is often troublesome. Communicating epidemiological statistics of these dermatophytes is greatly impeded because taxonomic schemes adopted by different research groups are inconsistent and hardly comparable. OBJECTIVES: To analyse the molecular types existing within isolates of the T. mentagrophytes complex in Taiwan and evaluate the applicability of the current taxonomy on these isolates. METHODS: Forty-eight isolates of the T. mentagrophytes complex were obtained from humans and animals (rabbit, guinea pig and hedgehog) in Taiwan. Sequences of ITS1-5.8S-ITS2 and b-tubulin gene regions of each isolate were used for molecular typing. RESULTS: Among the 48 isolates, 43 belonged to the T. interdigitale clade, including 21 of the anthropophilic strain and 22 of the zoophilic strain, and five belonged to the T. erinacei clade. No isolates of the T. mentagrophytes genotype were found. CONCLUSIONS: The isolates previously identified as T. mentagrophytes should be relabelled as T. interdigitale according to current taxonomy. Because the taxonomy is quite different from what it used to be, confusion in the nomenclature of the T. mentagrophytes complex is to be expected. The applicability of the current taxonomic concept may require further evaluation.

Transformation of dissolved organic matter by oxidative polymerization with horseradish peroxidase.

Dissolved organic matter (DOM) has significant influence on the transport and fate of contaminants in multiple phases and it has potential hazard by acting as a precursor of disinfection by-products in water supply. The changes in DOM characteristics, especially by oxidative polymerization might result in different behaviour in the interaction with many contaminants. The aim of this work was to verify the catalytic effects of peroxidase on oxidative polymerization of humic and fulvic substances by examination of the structural characteristics. Transformation of humic acid (HA) and fulvic acid (FA) by oxidative polymerization catalyzed by horseradish peroxidase and hydrogen peroxide were investigated. Size exclusion chromatography, excitation-emission matrices spectra (EEMs), synchronous fluorescence spectra, and infrared spectroscopy was used to evaluate the structural transformation of HA and FA. Molecular weight of HA and FA was continuously changed and their weight-average molecular weight (MWw) reached maximum after 8 h. The MWw of HA and FA were proportionally increased with a dosage of horseradish peroxidase and hydrogen peroxide, indicating that HA and FA was transformed into larger and complex molecules. Spectroscopic results indicated that HA and FA structure contains strong polycyclic aromatic structures with more aromatic rings and a higher degree of conjugation.

Diabetes mellitus and tuberculosis in Korean adults: impact on tuberculosis incidence, recurrence and mortality.

The prevalence of diabetes mellitus (DM) worldwide is increasing markedly, and many countries with rising rates also have a high incidence rate of tuberculosis (TB). To investigate the relationships of fasting serum glucose (FSG) and DM with TB incidence, recurrence and mortality risk in a prospective cohort study in South Korea. Our study comprised 1 267 564 Koreans who received health insurance from the National Health Insurance System, had an initial medical evaluation between 1997 and 2000 and were prospectively followed biennially. Participants with DM had a higher risk for incident TB (hazard ratio [HR] 1.81, 95%CI 1.71-1.91 in males, HR 1.33; 95%CI 1.20-1.47 in females) than those without DM. There was a strong positive trend for TB risk with rising FSG among males. The risk for recurrent TB among those with previous TB was significantly higher in males (HR 1.58, 95%CI 1.43-1.75) and in females with DM (HR 1.38, 95%CI 1.08-1.76). The increased risk of death from TB during follow-up was also significant in men (HR 1.91, 95%CI 1.87-1.95) and in women (HR 1.71, 95%CI 1.65-1.77). A diagnosis of DM is a risk factor for TB, TB recurrence and death from TB. Screening for TB should be considered among people living with DM in Korea, particularly those with severe DM. .

Involvement of matrix metalloproteinase-13 in stromal-cell-derived factor 1 alpha-directed invasion of human basal cell carcinoma cells.

Basal cell carcinoma (BCC) is one of the most common skin neoplasms in humans and is usually characterized by local aggressiveness with little metastatic potential, although deep invasion, recurrence, and regional and distant metastases may occur. Here, we studied the mechanism of BCC invasion. We found that human BCC tissues and a BCC cell line had significant expression of CXCR4, which was higher in invasive than non-invasive BCC types. Further, of 19 recurrent tumors among 390 BCCs diagnosed during the past 12 years, 17/19 (89.5%) had high CXCR4 expression. We found that the CXCR4 ligand, stromal-cell-derived factor 1alpha (SDF-1alpha), directed BCC invasion and that this was mediated by time-dependent upregulation of mRNA expression and gelatinase activity of matrix metalloproteinase-13 (MMP-13). The transcriptional regulation of MMP-13 by SDF-1alpha was mediated by phosphorylation of extracellular signal-related kinase 1/2 and activation of the AP-1 component c-Jun. Finally, CXCR4-transfected BCC cells injected into nude mice induced aggressive BCCs that co-expressed CXCR4 and MMP-13. The identification of SDF-1alpha/CXCR4 as an important factor in BCC invasiveness may contribute insight into mechanisms involved in the aggressive potential of human BCC and may improve therapy for invasive BCCs.

Neuro-mediators as predictors of paediatric atopic dermatitis.

BACKGROUND: Attempts to identify predictors of atopic dermatitis (AD) have focused on genetic and immunologic factors. However, the role of neuro-mediators remains to be elucidated. OBJECTIVE: To evaluate nerve growth factor (NGF) and vaso-active intestinal peptide (VIP) in predicting paediatric AD and assess their correlation with intrinsic and extrinsic types of AD. METHODS: We performed a nested case-control study in the prospective Taiwan birth panel cohort study. Cord and maternal plasma and questionnaires were gathered at birth. During follow-up, we identified 40 available AD cases, which were matched to 80 unaffected controls chosen from this cohort. The concentrations of IgE, NGF, and VIP in cord and maternal plasma of these subjects were performed by ELISA. Receiver-operating characteristic (ROC) curves were generated to see how well each biomarker could predict AD. RESULTS: The NGF levels were significantly higher in AD patients than controls (mean+/-SD: 65.47+/-44.45 vs. 49.21+/-12.18 pg/mL for cord plasma and 89.68+/-41.04 vs. 66.96+/-23.05 pg/mL for maternal plasma) (P<0.05). VIP levels were also higher but not statistically significant. Plasma NGF may be a better biomarker than IgE in detecting paediatric AD (area under the ROC curve=0.65 vs. 0.61 for cord plasma and 0.69 vs. 0.61 for maternal plasma). Maternal NGF levels were significantly higher in patients with both intrinsic (96.18+/-48.15 pg/mL) and extrinsic (86.18+/-37.23 pg/mL) types of AD compared with controls (66.96+/-23.05 pg/mL) (P<0.05). We assessed a significant correlation between self-reported stress during pregnancy and maternal NGF levels (r=0.22, P=0.02). CONCLUSION: Our results suggest that NGF is a good alternative biomarker in predicting children with a risk of AD.

Overexpression of interleukin-6 in human basal cell carcinoma cell lines increases anti-apoptotic activity and tumorigenic potency.

Interleukin-6 (IL-6) is a pleiotropic cytokine that is capable of modulating the diverse functions of cells such as acute phase responses and inflammation. Excessive or insufficient production of IL-6 may contribute to certain diseases of the skin. The aim of this study was to investigate the possible role of IL-6 in the tumorigenesis of basal cell carcinoma (BCC). Initially, we transfected IL-6 expression vector, under the control of a CMV promoter, into human BCC cells and successfully obtained IL-6-overexpressing clones (BCC/IL-6-c1 and BCC/IL-6-c2) and a mixture (BCC/IL-6). DNA synthesis assay determined using (3)H-thymidine pulse incorporation revealed that IL-6-expressing BCC cells exhibited a much higher DNA synthesis rate than the neo control or parental BCC cells. We also detected a greater abundance of IL-6-expressing cell colonies formed in soft agar than in the vector control cells. Furthermore, BCC/IL-6 cells, but not vector control cells, were resistant to UV and photodynamic therapy (PDT)-induced apoptosis, as confirmed using DNA fragmentation and morphologic change analyses. Immunoblot analysis showed that Mcl-1, an anti-apoptotic protein, was specifically up-regulated IL-6 transfectants but not in the control cells. Transient transfection of IL-6 transfectants with antisense mcl-1 greatly enhanced their apoptosis frequency by UV treatment. In tumorigenesis assay, IL-6 transfected clones formed tumors in nude mice more rapidly than the control cells. These tumors appeared to be highly vascularized using pathological examination. Supportive of this finding, we found that IL-6 transfected cells expressed elevated levels of two angiogenic factors, cyclooxygenase (Cox)-2 and vascular endothelial growth factor (VEGF). These results suggest that overexpression of IL-6 enhances the tumorigenic activity of BCC cells by both suppressing apoptosis and actively promoting angiogenesis.

Effect of dietary patterns on serum homocysteine: results of a randomized, controlled feeding study.

BACKGROUND: Elevated blood levels of homocysteine are associated with an increased risk of atherosclerotic cardiovascular disease. Although numerous studies have assessed the impact of vitamin supplements on homocysteine, the effect of dietary patterns on homocysteine has not been well studied. METHODS AND RESULTS: During a 3-week run-in, 118 participants were fed a control diet, low in fruits, vegetables, and dairy products, with a fat content typical of US consumption. During an 8-week intervention phase, participants were then fed 1 of 3 randomly assigned diets: the control diet, a diet rich in fruits and vegetables but otherwise similar to control, or a combination diet rich in fruits, vegetables, and low-fat dairy products and reduced in saturated and total fat. Between the end of run-in and intervention periods, mean change in homocysteine was +0.46 micromol/L in the control diet, +0.21 micromol/L in the fruits and vegetables diet (P=0.47 compared with control), and -0.34 micromol/L in the combination diet (P=0.03 compared with control, P=0.12 compared with the fruits and vegetables diet). In multivariable regression models, change in homocysteine was significantly and inversely associated with change in serum folate (P=0.03) but not with change in serum vitamin B(12) (P=0.64) or pyridoxal 5' phosphate, the coenzyme form of vitamin B(6) (P=0.83). CONCLUSIONS: Modification of dietary patterns can have substantial effects on fasting levels of total serum homocysteine. These results provide additional insights into the mechanisms by which diet might influence the occurrence of atherosclerotic cardiovascular disease.

Curcumin induces a p53-dependent apoptosis in human basal cell carcinoma cells.

Curcumin, a potent antioxidant and chemopreventive agent, has recently been found to be capable of inducing apoptosis in human hepatoma and leukemia cells by way of an elusive mechanism. Here, we demonstrate that curcumin also induces apoptosis in human basal cell carcinoma cells in a dose- and time-dependent manner, as evidenced by internucleosomal DNA fragmentation and morphologic change. In our study, consistent with the occurrence of DNA fragmentation, nuclear p53 protein initially increased at 12 h and peaked at 48 h after curcumin treatment. Prior treatment of cells with cycloheximide or actinomycin D abolished the p53 increase and apoptosis induced by curcumin, suggesting that either de novo p53 protein synthesis or some proteins synthesis for stabilization of p53 is required for apoptosis. In electrophoretic mobility gel-shift assays, nuclear extracts of cells treated with curcumin displayed distinct patterns of binding between p53 and its consensus binding site. Supportive of these findings, p53 downstream targets, including p21(CIP1/WAF1) and Gadd45, could be induced to localize on the nucleus by curcumin with similar p53 kinetics. Moreover, we immunoprecipitated extracts from basal cell carcinoma cells with different anti-p53 antibodies, which are known to be specific for wild-type or mutant p53 protein. The results reveal that basal cell carcinoma cells contain exclusively wild-type p53; however, curcumin treatment did not interfere with cell cycling. Similarly, the apoptosis suppressor Bcl-2 and promoter Bax were not changed with the curcumin treatment. Finally, treatment of cells with p53 antisense oligonucleotide could effectively prevent curcumin-induced intracellular p53 protein increase and apoptosis, but sense p53 oligonucleotide could not. Thus, our data suggest that the p53-associated signaling pathway is critically involved in curcumin-mediated apoptotic cell death. This evidence also suggests that curcumin may be a potent agent for skin cancer prevention or therapy.

The phosphotidyl inositol 3-kinase/Akt signal pathway is involved in interleukin-6-mediated Mcl-1 upregulation and anti-apoptosis activity in basal cell carcinoma cells.

Dysregulation of interleukin-6 has been reported to be associated with various types of tumors, and interleukin-6 plays an important part in regulating apoptosis in many types of cells. Previously, Mcl-1 was shown to be significantly increased in interleukin-6-overexpressed basal cell carcinoma cells and conferred on them anti-apoptotic activity. The aim of this study was to investigate which signaling pathway is involved in the anti-apoptotic effect of interleukin-6 on basal cell carcinoma cells. Here we show that the addition of recombinant 100 ng per ml interleukin-6 to basal cell carcinoma cells induced a 2.3-fold increase in the level of Mcl-1 protein in basal cell carcinoma cells. Transfection with dominant-negative STAT3 (STAT3F) into inter-leukin-6-treated basal cell carcinoma cells caused a decrease of phosphotyrosyl STAT3 but did not alter Mcl-1 protein levels; however, AG490, a Janus tyrosine kinase inhibitor, was capable of inhibiting the interleukin-6-induced elevation of Mcl-1 protein. Next, interleukin-6 stimulation elicited extracellular signal-regulated kinase activation in basal cell carcinoma cells, and the mitogen-activated protein kinase inhibitor, PD98059, could affect this response without affecting the interleukin-6-medi-ated Mcl-1 upregulation. Use of the two phosphotidyl inositol 3-kinase inhibitors, LY294002 and wortmannin, to check whether this pathway is involved in Mcl-1 upregulation by interleukin-6, we found that the phosphotidyl inositol 3-kinase inhibitors completely attenuated the interleukin-6-induced Mcl-1 upregulation. Furthermore, in the interleukin-6-overexpressing basal cell carcinoma cell clone, dominant-negative Akt also significantly reduced the increased level of Mcl-1. Interestingly, Janus tyrosine kinase inhibitor, AG490, treatment strongly blocked the phosphotidyl inositol 3-kinase pathway activation, as evidenced by the decrease in phospho-Akt level. Blockage of phosphotidyl inositol 3-kinase/Akt pathway abolished the interleukin-6-mediated anti-apoptotic activity in ultraviolet B treated cells. Unexpectedly, without ultraviolet B irradiation, STAT3F transfection also induced a significant apoptosis in basal cell carcinoma/interleukin-6 cells. Taken together, our data suggest that both the phosphotidyl inositol 3-kinase/Akt and STAT3 pathways are potentially involved in interleukin-6-mediated cell survival activity in basal cell carcinoma cells; however, the upregulation of the anti-apoptotic Mcl-1 protein by interleukin-6 is mainly through the Janus tyrosine kinase/phosphotidyl inositol 3-kinase/Akt, but not the STAT3 pathway.

The effect of chronic coffee drinking on blood pressure: a meta-analysis of controlled clinical trials.

We sought to assess the effect of coffee consumption on blood pressure in humans. Our data sources included a MEDLINE search of the literature published before December 1997, bibliography review, and expert consultation. We selected controlled trials in which coffee consumption was the only difference between the intervention and control groups, mean blood pressure change was reported for each group or period, and treatment lasted for >24 hours. Of 36 studies initially identified, 11 (522 participants) met these inclusion criteria. Information on sample size, study design, participant characteristics (gender, race, age, baseline blood pressure, and antihypertensive medications), and treatment results were abstracted by 3 reviewers using a standardized protocol. Treatment effect of coffee consumption on blood pressure was estimated with the use of a random-effects model. In the 11 trials, median duration was 56 days (range, 14 to 79 days), and median dose of coffee was 5 cups/d. Systolic and diastolic blood pressure increased by 2.4 (range, 1.0 to 3.7) mm Hg and 1.2 (range, 0.4 to 2.1) mm Hg, respectively, with coffee treatment compared with control. Multiple linear regression analysis identified an independent, positive relationship between cups of coffee consumed and subsequent change in systolic blood pressure, independent of age of study participants and study design characteristics. The effect of coffee drinking on systolic and diastolic blood pressure was greater in trials with younger participants. Our findings provide support for a relationship between coffee consumption and higher blood pressure. Trials of coffee cessation of longer duration and in persons with hypertension should be performed.

Plasma fibronectin levels in ischemic heart disease.

Fibronectin is a paradigm adhesive protein which has been implicated in the regulation of several cellular processes and cell-cell interactions. Large amounts of fibronectin have been detected in atherosclerotic plaques, while hypertension in animal models has been shown to rapidly increase fibronectin expression in arterial walls. The aim of the present study was to determine the levels of plasma fibronectin (FN) in 133 patients with ischemic heart disease and in 36 normal controls, and to investigate the possible association with blood pressure. Plasma FN levels in patients with ischemic heart disease were found to be significantly elevated (mean+/-S.D.; 46.5+/-14.2 mg/dl) compared with the control group (38.0+/-14.2 mg/dl) (P=0.002). Plasma FN concentrations were significantly different between the hypertensive group (52.9+/-14.5 mg/dl) and the normal blood pressure group (41.4+/-11.8 mg/dl) among the patients with ischemic heart disease (P<0.001). Plasma FN concentration was positively correlated with total cholesterol, triglyceride, systolic blood pressure and body mass index. In conclusion, the plasma fibronectin level may have pathogenetic implications in association with lipid components and blood pressure in patients with ischemic heart disease.

The methylenetetrahydrofolate reductase gene is associated with increased cardiovascular risk in Japan, but not in other populations.

The methylenetetrahydrofolate reductase (MTHFR) gene has been associated with increased risk for cardiovascular disease in some, but not all studies. Our data sources included a MEDLINE search of the literature published before December 1998, a bibliography review, and expert consultation. Of 23 studies initially identified, 18 (9855 persons) met the inclusion criteria. Information on sample size, study design, Hardy-Weinberg equilibrium, method of genotype determination, plasma folate and homocysteine were abstracted by two reviewers using a standardized protocol. The overall odds ratio of the MTHFR gene on cardiovascular disease was estimated using the Mantel-Haenzel method. From 12 studies with angiographically-confirmed coronary artery disease (CAD), the overall odds ratio (OR) for CAD among those with heterozygous (V/A) was 1.3 (95% CI, 1.1-1.5), while it was 1.4 (1.2-1.6) for the homozygous mutant (V/V) compared to those with homozygous normal (A/A). However, the overall odds ratio for CAD among those with the V/V genotype versus A/A genotype was not statistically significant (OR: 1.1; 95% CI: 0.9-1.3) after excluding three Japanese studies. The corresponding OR for the three Japanese studies was 2.0 (1.6-2.7). For six studies with myocardial infarction (MI), the overall OR of MI was 1.0 (0.8-1.1) for those with the V/A genotype and 0.9 (0.7-1.1) for those with the V/V genotype, respectively; none of these ORs for MI was statistically significant. The MTHFR gene is associated with increased risk for CAD in Japan, but not in other populations.

Arsenic-related Bowen's disease and paraquat-related skin cancerous lesions show no detectable ras and p53 gene alterations.

We have investigated point mutations of codons 12, 13, and 61 in H-, K-, and N-ras oncogenes as well as p53 tumour suppressor gene exon 5 through exon 9 by PCR-SSCP analysis in 26 skin biopsy tissues from 16 arsenic-related Bowen's disease patients and 6 skin samples from 4 paraquat manufacturing workers. No mutation was found. These results are different from findings with UV associated skin cancers. Interestingly, a silent change at codon 27 of H-ras in one allele was detected in all 4 paraquat manufacturing workers and in 2 of 16 arsenic-related Bowen's disease patients. It is likely that the molecular mechanisms involved in arsenic and paraquat induced skin cancers differ from sunlight-related skin malignancies.