Serum pro-BDNF/BDNF as a treatment biomarker for response to docosahexaenoic acid in traumatized people vulnerable to developing psychological distress: a randomized controlled trial.

Our open-label pilot study showed that supplementation with docosahexaenoic acid (DHA) increased serum brain-derived neurotrophic factor (BDNF) levels and that there might be an association between changes in serum BDNF levels and reduced psychological distress. Animal research has indicated that a DHA-enriched diet increases BDNF in the brain. In this randomized double-blind controlled trial of severely injured patients vulnerable to posttraumatic stress disorder (PTSD) and depression, we examined whether DHA increases serum BDNF levels and whether changes in BDNF levels are associated with subsequent symptoms of PTSD and depression. Patients received 1470 mg per day of DHA plus 147 mg per day of eicosapentaenoic acid (EPA; n = 53) or placebo (n = 57) for 12 weeks. Serum levels of mature BDNF and precursor pro-BDNF at baseline and 12-week follow-up were measured using enzyme-linked immunosorbent assay kits. At 12 weeks, we used the Clinician-Administered PTSD Scale to assess PTSD symptoms and depressive symptoms by the Montgomery-Åsberg Depression Rating Scale. We found a significant increase in serum BDNF levels during the trial in the DHA and placebo groups with no interaction between time and group. Changes in BDNF levels were not associated with PTSD severity but negatively associated with depression severity (Spearman's ρ = -0.257, P = 0.012). Changes in pro-BDNF were also negatively associated with depression severity (Spearman's ρ = -0.253, P = 0.013). We found no specific effects of DHA on increased serum levels of BDNF and pro-BDNF; however, evidence in this study suggests that increased BDNF and pro-BDNF have a protective effect by minimizing depression severity.

Phase II trial of gefitinib alone without radiation therapy for Japanese patients with brain metastases from EGFR-mutant lung adenocarcinoma.

BACKGROUND: Brain metastases (BM) are a common in patients with lung cancer. Although whole-brain radiation therapy (WBRT) is the standard therapy, it may have a risk of decline in cognitive function of patients. In this study, we evaluated the efficacy of gefitinib alone without radiation therapy for the treatment of patients with BM from lung adenocarcinoma. MATERIALS AND METHODS: Eligible patients had BM from lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations. Gefitinib was given at 250 mg orally once a day until tumor progression or unacceptable toxicity. RESULTS: Forty-one patients were enrolled. The response rate was 87.8%. No patient experienced grade ≥4 toxicity. The median progression-free survival time was 14.5 months (95% CI, 10.2-18.3 months), and the median overall survival time was 21.9 months (95% CI, 18.5-30.3 months). In compared with L858R, exon 19 deletion was associated with better outcome of patients after treatment with gefitinib in both progression-free (p = 0.003) and overall survival (p = 0.025). CONCLUSION: Favorable response of BM to gefitinib even without irradiation was demonstrated. Exon 19 deletion was both a predictive and prognostic marker of patients with BM treated by gefitinib.

High CC chemokine receptor 7 expression improves postoperative prognosis of lung adenocarcinoma patients.

BACKGROUND: Chemokines and chemokine receptors not only have significant roles in cancer metastasis and tumorigenesis but also act as antitumour agents. The interaction between the Crk-like adaptor protein (CrkL), which is encoded by the CRKL gene, and non-receptor tyrosine kinase c-ABL is reported to transform many cells into malignant cells. We examined the effects of CC chemokine receptor 7 (CCR7), CCR7 ligands and CrkL and c-ABL in lung adenocarcinoma. METHODS: One hundred and twenty patients with lung adenocarcinoma were included in this historical cohort analysis. We examined CCR7 and CCR7 ligands and CrkL and c-ABL mRNA expressions in surgically resected lung adenocarcinoma specimens and evaluated their contribution to prognosis, and the relationship with epidermal growth factor receptor (EGFR) and TP53 mutations. RESULTS: High CCR7 mRNA expressions indicated better prognoses than those of the groups with low CCR7 mRNA expressions (P=0.007, HR=2.00, 95% CI of ratio: 1.22 -3.31). In lung adenocarcinoma, CrkL and c-ABL mRNAs were related to CCR7 mRNA expression (P<0.0001). CrkL and c-ABL mRNA expressions were influenced by EGFR mutations. A high expression of CCL19 was a good prognostic factor of lung adenocarcinoma. CONCLUSION: We propose that CCR7 and CCL19 are clinically good prognostic factors and that CCR7 is strongly related to CrkL and c-ABL kinase mRNA expression in lung adenocarcinoma.

Solution softening in magnesium alloys: the effect of solid solutions on the dislocation core structure and nonbasal slip.

There is a pressing need to improve the ductility of magnesium alloys so that they can be applied as lightweight structural materials. In this study, a mechanism for enhancing the ductility of magnesium alloys has been pursued using the atomistic method. The generalized stacking fault (GSF) energies for basal and prismatic planes in magnesium were calculated by using density functional theory, and the effect of the GSF energy on the dislocation core structures was examined using a semidiscrete variational Peierls-Nabarro model. Yttrium was found to have an anomalous influence on the solution softening owing to a reduction in the GSF energy gradient.

Efficacy of the lidocaine/flurbiprofen axetil combination for reducing pain during the injection of propofol.

BACKGROUND: Pain during the injection of propofol is a common clinical problem. Lidocaine pretreatment, preceded by venous occlusion, is the most popular method for reducing pain during the injection of propofol but cannot entirely control such pain. We aimed to evaluate the efficacy of lidocaine, flurbiprofen axetil (an injectable prodrug of flurbiprofen), and the two in combination for reducing pain during the injection of propofol. METHODS: This prospective, randomized, double-blind, placebo-controlled study was conducted at the Department of Anesthesiology, Ushiku Aiwa General Hospital, Ibaraki, Japan. One hundred patients, 55 men and 45 women aged 22-69 years old and with ASA physical statuses of I-II, were randomly allocated to one of four groups to receive intravenously placebo (saline), lidocaine 40 mg, flurbiprofen axetil 50 mg, or both (N=25 for each group), with venous occlusion for 2 minutes, followed by administration of propofol 0.5 mg/kg into a dorsal hand vein. A blind researcher asked the patients to assess pain during injection of propofol. RESULTS: The treatment groups were comparable with respect to patient characteristics. The overall incidence of propofol-induced pain was 32% with lidocaine (P=0.001), 40% with flurbiprofen axetil (P = 0.001), and 8% with both (P=0.001), compared with 88% with placebo. The incidence of such pain was lower in patients receiving the lidocaine/flurbiprofen axetil combination than in those receiving lidocaine or flurbiprofen (P=0.036, combination vs. lidocaine; P=0.009, combination vs. flurbiprofen axetil). CONCLUSION: The lidocaine/flurbiprofen axetil combination, compared with lidocaine 40 mg or flurbiprofen 50 mg, effectively reduces pain during the injection of propofol.

Reduction of postoperative nausea, vomiting, and analgesic requirement with dexamethasone for patients undergoing laparoscopic cholecystectomy.

BACKGROUND: Dexamethasone has antiemetic and analgesic effects for various types of surgery. The efficacy of dexamethasone for reducing postoperative nausea and vomiting (PONV) and analgesic requirement has never been evaluated for patients undergoing laparoscopic cholecystectomy (LC). METHODS: In a prospective, randomized, double-blind, placebo-controlled study, patients intravenously received placebo, dexamethasone 4 mg, or dexamethasone 8 mg immediately before induction of anesthesia. A standard anesthetic technique, including sevoflurane and air in oxygen, was used. Postoperatively, emetic symptoms (nausea, retching, and vomiting) and analgesic requirement were evaluated by an investigator. RESULTS: The study enrolled 90 patients (38 men and 52 nonpregnant women), with each treatment group comprising 30 patients. The rate of patients experiencing PONV 0-24 h after anesthesia was 60% for the dexamethasone 4 mg group (p = 0.294) and 33% for the dexamethasone 8 mg group (p = 0.01), compared with 70% for the placebo group. The need for indomethacin to relieve intolerable pain was less in the dexamethasone 8 mg group than in the placebo group (p = 0.008) or the dexamethasone 4 mg group (p = 0.029). No difference in analgesic requirement was found between the dexamethasone 4 mg group and the placebo group (p = 0.395). No clinically important adverse effects due to the study drug were observed in any group. CONCLUSIONS: Prophylactic therapy with dexamethasone 8 mg is effective in reducing PONV and analgesic requirement for patients undergoing LC.

Association study of TRAF1-C5 polymorphisms with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in Japanese.

OBJECTIVE: The primary aim of this study was to investigate the association of polymorphisms of TRAF1-C5, a newly identified rheumatoid arthritis (RA) risk locus in Caucasians, with susceptibility to RA and systemic lupus erythematosus (SLE) in Japanese populations. Gene expression levels of TRAF1 and C5 to assess the functional significance of genotypes were also analysed. METHODS: A multicentre association study consisting of 4 RA case-control series (4397 cases and 2857 controls) and 3 SLE case-control series (591 cases and 2199 shared controls) was conducted. Genotyping was performed using TaqMan genotyping assay for two single nucleotide polymorphisms (SNPs) that showed the best evidence of association in the previous Caucasian studies. Quantifications of TRAF1 and C5 expression were performed with TaqMan expression assay. RESULTS: Significant differences in allele frequency for both SNPs were observed between RA and control subjects (combined odds ratio = 1.09), while no significant difference was detected between patients with SLE and controls. Interestingly, alleles rs3761847 A and rs10818488 G had increased the risk for RA in the present study, while they decreased the risk in the original studies. A significant difference was found between risk allele carriers and non-carriers of rs10818488 for the expression level of TRAF1 in phorbol myristate acetate-stimulated lymphoblastoid cell lines (p = 0.04). CONCLUSION: Association of TRAF1-C5 locus with RA susceptibility was detected in the Japanese populations with modest magnitude, while no significant association was observed for SLE. Significant positive effect of genotype on the expression of TRAF1 might support the genetic association between TRAF1 and RA.

Microstructure analysis of Nd-Fe-B sintered magnets improved by Tb-metal vapour sorption.

Behaviours of constituent elements in the Nd-Fe-B sintered magnets improved by Tb-metal vapour sorption have been investigated by using an analytical transmission microscopy. It was found that a triple junction of the grain boundaries consists of fine Nd-O crystalline and amorphous phase. The energy dispersive X-ray spectroscopy (EDS) analysis showed that the amorphous phase mainly consists of Co, Nd and Tb. The Tb-treatment causes the formation of the amorphous Co-Nd(Tb) wetting-layer phase which wraps each Nd(2)Fe(14)B grain. The results suggest that the wrapped structure prevents the nucleation of magnetic reversed domains and then improves significantly the coercivity of the magnet.

Ferromagnetism and electronic structures of nonstoichiometric Heusler-alloy Fe3-xMnxSi Epilayers grown on Ge(111).

For the study of ferromagnetic materials which are compatible with group-IV semiconductor spintronics, we demonstrate control of the ferromagnetic properties of Heusler-alloy Fe3-xMnxSi epitaxially grown on Ge(111) by tuning the Mn composition x. Interestingly, we obtain L2(1)-ordered structures even for nonstoichiometric atomic compositions. The Curie temperature of the epilayers with x approximately 0.6 exceeds 300 K. Theoretical calculations indicate that the electronic structures of the nonstoichiometric Fe3-xMnxSi alloys become half-metallic for 0.75 < or = x < or = 1.5. We discuss the possibility of room-temperature ferromagnetic Fe(3-x)Mn(x)Si/Ge epilayers with high spin polarization.

The association of genetic variants in Krüppel-like factor 11 and Type 2 diabetes in the Japanese population.

AIMS: Krüppel-like factor 11 (KLF11) is a transcriptional factor of the zinc finger domain family that regulates the expression of insulin. In North European populations, its common functional variant Q62R (rs35927125) is a strong genetic factor for Type 2 diabetes (P = 0.00033, odds ratio for G allele = 1.29, 95% CI 1.12-1.49). We examined the contribution of KLF11 variants to the susceptibility to Type 2 diabetes in a Japanese population. METHODS: By re-sequencing Japanese individuals (n = 24, partly 96), we screened all four exons, exon/intron boundaries and flanking regions of KLF11. Verified single nucleotide polymorphisms (SNPs) were genotyped in 731 initial samples (369 control and 362 case subjects). Subsequently, we tested for association in 1087 samples (524 control and 563 case subjects), which were collected in different districts of Japan from the initial samples. RESULTS: We identified eight variants, including a novel A/C variant on intron 3, but no mis-sense mutations. In an association study, we failed to find any significant result of SNPs (minor allele frequency 8.2-46.2%) after correcting for multiple testing. Similarly, no haplotypes were associated with Type 2 diabetes. It is notable that the G allele in rs35927125 was completely absent in 1818 Japanese individuals. CONCLUSIONS: Genetic variants in KLF11 are unlikely to have a major effect of Type 2 diabetes in the Japanese population, although they were significantly associated in North European populations. These observations might help to determine the role of KLF11 variants in Type 2 diabetes in different populations.

Parafibromin tumor suppressor enhances cell growth in the cells expressing SV40 large T antigen.

Parafibromin (PF) is a 531-amino acid protein encoded by HRPT2, a putative tumor suppressor gene recently implicated in the autosomal-dominant hyperparathyroidism-jaw tumor familial cancer syndrome and sporadic parathyroid carcinoma. To investigate effects of PF's overexpression on cell proliferation, we performed assays in four different cell lines. The transient overexpression of PF inhibited cell growth in HEK293 and NIH3T3 cells, but enhanced cell growth in the SV40 large T antigen-expressing cell lines such as 293FT and COS7 cells. In 293FT cells, PF was found to interact with SV40 large T antigen and its overexpression promoted entry into the S phase, implying that the interaction enhanced progression through the cell cycle. The tumor suppressor protein PF acts as a positive regulator of cell growth similar to an oncoprotein in the presence of SV40 large T antigen.

Genetic association of single nucleotide polymorphisms in endonuclease G-like 1 gene with type 2 diabetes in a Japanese population.

AIMS/HYPOTHESIS: In order to identify type 2 diabetes disease susceptibility gene(s) in a Japanese population, we applied a region-wide case-control association test to the 20.4 Mb region between D3S1293 and D3S2319 on chromosome 3p24.3-22.1, supported by linkage to type 2 diabetes and its related traits in Japanese and multiple populations. MATERIALS AND METHODS: We performed a two-stage association test using 1,762 Japanese persons with 485 gene-centric, evenly spaced, common single nucleotide polymorphism (SNP) markers with minor allele frequency >0.1. For mouse studies, total RNA was extracted from various organs of BKS.Cg-+Lepr(db)/+Lepr(db) and control mice, and from MIN6, NIH3T3 and C2C12 cell lines. RESULTS: We detected a landmark SNP375 (A/G) (rs2051211, p = 0.000046, odds ratio = 1.33, 95% CI 1.16-1.53) in intron 5 of the endonuclease G-like 1 (ENDOGL1) gene. Systematic dense SNPs approach identified a susceptibility linkage disequilibrium (LD) block of 116.5 kb by |D'|, an LD units map and a critical region of 2.1 kb by r (2) in ENDOGL1. A haplotype-based association test showed that an at-risk haplotype is associated with disease status (p = 0.00001). The expression of ENDOGL1 was rather ubiquitous with relatively abundant expression in the brain and also in a pancreatic islet beta cell line. Mouse Endogl1 expression increased in pancreatic islets of hyperglycaemic BKS.Cg-+Lepr(db)/+Lepr(db) mice compared with that in control mice. CONCLUSIONS/INTERPRETATION: Based on the population genetics, fine mapping of LD block and haplotype analysis, we conclude that ENDOGL1 is a candidate disease-susceptibility gene for type 2 diabetes in a Japanese population. Further analysis in a larger sample size is required to substantiate this conclusion.

Interaction between catechol-O-methyltransferase (COMT) Val108/158Met and brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms in age at onset and clinical symptoms in schizophrenia.

Catechol-O-methyltransferase (COMT) gene is one of the candidate genes for schizophrenia because it codes an enzyme that participates in the metabolic inactivation of dopamine and noradrenaline and a limiting factor of dopamine metabolism in the prefrontal cortex. COMT gene lies on chromosome 22q11.2, which has been associated with schizophrenia susceptibility. A single-nucleotide polymorphism of COMT gene at position 108/158 results in an amino acid substitution from valine (val) to methionine (met), which modifies its enzymatic activity and may change the brain morphology and expressional behaviors. On the other hand, brain-derived neurotrophic factor (BDNF) plays a critical role in the development of mesolimbic dopaminergic- related systems. BDNF also contains a functional single-nucleotide polymorphism at codon 66 (Val66Met) of its prodomain and this polymorphism is responsible for schizophrenia susceptibility. In this study, we first investigated the relationship between COMT Val108/158Met polymorphism and age at onset as well as levels of clinical symptoms in 158 of chronic schizophrenia inpatients and then we investigated the gene-by-gene interaction between COMT Val108/158Met polymorphism and BDNF Val66Met polymorphism with age- and sex-matched control subjects (n = 318). We concluded that the COMT Val108/158Met polymorphism was not related to either the onset at age or the levels of clinical symptoms after long-term antipsychotic treatment in schizophrenia.

Branching mechanism of intergranular crack propagation in three dimensions.

We investigate the process of slow intergranular crack propagation by the finite element method model and show that branching is induced by partial arresting of a crack front owing to the geometrical randomness of grain boundaries. A possible scenario for the branching instability of crack propagation in a disordered continuous medium is also discussed.

In vivo proliferation of differentiated pancreatic islet beta cells in transgenic mice expressing mutated cyclin-dependent kinase 4.

AIMS/HYPOTHESIS: It has previously been hypothesised that highly differentiated endocrine cells do not proliferate or regenerate. However, recent studies have revealed that cyclin-dependent kinase 4 (CDK4) is necessary for the proliferation of pancreatic islet beta cells. The aim of this study was to determine whether activation of CDK4 can potentially be used as a radical treatment for diabetes without malignant transformation. METHODS: We generated transgenic mice expressing mutant CDK4 under the control of the insulin promoter to examine the effect of activated CDK4 overexpression in the postnatal development of pancreatic islets. RESULTS: In the transgenic mice, total CDK4 protein expression was increased by up to 5-fold, with a concomitant increase in CDK4 activity indicated by the detection of phosphorylated Rb protein in pancreatic islets. Histopathologically, many cells tested positive for proliferating cell nuclear antigen, and pancreatic islets displayed hyperplasia due to the extreme proliferation of beta cells containing a large number of insulin granules. Pancreatic islet alpha, delta and PP cells did not increase. Over an 18-month observation period, the transgenic mice did not develop insulinoma. Levels of expression of GLUT1 and c-myc were comparable to those in the littermates of the transgenic mice. GLUT2 expression was identified in the pancreatic islets of transgenic mice. No significant differences in telomerase activities were detected between transgenic mice and their littermates. Transgenic mice were superior to their littermates in terms of glucose tolerance and insulin secretion in response to the intraperitoneal injection of glucose, and hypoglycaemia was not observed. CONCLUSIONS/INTERPRETATION: Activated CDK4 stimulates postnatal pancreatic beta cell proliferation, during which the highly differentiated phenotypes of pancreatic islet beta cells are preserved without malignant transformation.

Redox state-dependent and sorbitol accumulation-independent diabetic albuminuria in mice with transgene-derived human aldose reductase and sorbitol dehydrogenase deficiency.

AIMS/HYPOTHESIS: We investigated the role played by sorbitol accumulation in the kidney in the development of diabetic albuminuria. METHODS: We created mice ( hAR-Tg:SDH null) with transgene-derived human aldose reductase and sorbitol dehydrogenase (SDH) deficiency, and analysed (i). the contribution of accumulated sorbitol to urinary albumin excretion rate, and (ii). the effect of the aldose reductase inhibitor, epalrestat, on the diabetic redox state, including decreased renal reduced glutathione concentrations or increased lactate to pyruvate ratios in the diabetic kidney. RESULTS: Compared to littermates, non-diabetic transgenic mice had a 2.6-fold increase in aldose reductase mRNA. In a diabetic group, aldose reductase mRNA in hAR-Tg mice was 2.7-fold higher than in littermates. In the diabetic and non-diabetic groups, hAR-Tg:SDH null mice had the highest sorbitol content among all four genetic types including hAR-Tg:SDH null, SDH null, hAR-Tg and littermates. The urinary albumin excretion rate in non-diabetic groups was similar in the four genetic types of mouse. In diabetic groups it was greater than in non-diabetic groups, but did not correlate with the sorbitol content among the four genetic types of mouse. When aldose reductase inhibitor and streptozotocin were given simultaneously at 6 weeks of age, epalrestat prevented diabetic increases in urinary albumin excretion rate and completely prevented diabetic decreases in reduced glutathione concentrations and diabetic increases in lactate to pyruvate ratios, even in the presence of transgenic aldose reductase. CONCLUSIONS/INTERPRETATION: The degree of diabetic albuminuria in genetically modified mice is dependent on the redox state and independent of polyol accumulation; aldose reductase inhibitor can prevent diabetic albuminuria by normalising diabetic redox changes.

Mode of inheritance of HLA-DRB1 shared epitope in Japanese familial rheumatoid arthritis.

OBJECTIVE: To clarify the mode of genetic contribution of the HLA-DR shared epitope (SE) to the pathogenesis of familial cases of Japanese rheumatoid arthritis (RA). METHODS: Fifty-three unrelated Japanese RA families that had more than 2 affected sibs were selected. The HLA-DR shared epitope typing was carried out by the PCR method and PCR-SSCP (single stranded DNA conformation polymorphism) method. Affected sib pair analysis was carried out using the MAPMAKER/SIB 2.0 program. The mode of inheritance was also calculated based on the sharing of genes identical by descent (IBD) between siblings in each of the 53 affected sib-pairs (propositus and the 2nd affected sib). RESULTS: The maximum LOD score of HLA-DR was 0.437, and the sharing of 2 IBDs, 1 IBD, and no IBDs between affected sibs were 0.330, 0.500, and 0.170, respectively. The sharing distribution of IBD was confirmed to be compatible with the dominant or additive mode since the observed gene frequency of SE was 0.255. CONCLUSION: The HLA-DR shared epitope participated in the pathogenesis of familial cases of Japanese RA. The SE contributes to this pathogenesis in either the dominant or additive mode of inheritance.

Effect of triacylglycerols containing medium- and long-chain fatty acids on body fat accumulation in rats.

Effect of triacylglycerols containing medium- and long-chain fatty acids (TML) on body fat accumulation was studied in rats. Male Wistar rats were fed an experimental diet containing 25% soybean oil or TML for 6 weeks. The food intake for 6 weeks did not significantly differ between the two diet groups. However, the perirenal and mesenteric adipose tissue weight and carcass fat content were significantly lower in the TML diet group than in the soybean oil diet group. The epididymal adipose tissue weight and liver triacylglycerol content did not significantly differ between the two diet groups. The digestibility of dietary fat did not significantly differ between the two diet groups. These results suggest that an intake of TML decreases body fat accumulation compared to an intake of soybean oil in rats.

Plant polysaccharide PSK: cytostatic effects on growth and invasion; modulating effect on the expression of HLA and adhesion molecules on human gastric and colonic tumor cell surface.

PSK is a plant polysaccharide widely used for cancer immunotherapy in Japan and other Asian countries. It is considered that its antitumor effect is derived from its immunomodulating activity on the tumor-bearing host. The present study was designed to assess the direct action of PSK on in vitro proliferation and invasion of human KATO-3 gastric and Colo205 colonic cancer cell lines, and the expression of surface molecules such as HLA and adhesion molecules on these cells. The in vitro growth of KATO-3 cells was significantly inhibited by 100 micrograms/ml of PSK 48 hrs after culture initiation, and that of Colo205 was significantly inhibited by 10 and 100 micrograms/ml of PSK 24 hrs after culture initiation. The effect of PSK on the in vitro invasion of the tumor cells, assessed with a Matrigel invasion chamber, revealed that invasion of KATO-3 and Colo205 cells was inhibited by more than 10 micrograms/ml and more than 5 micrograms/ml of PSK, respectively. KATO-3 cells expressed HLA-ABC, HLA-A2/A28, HLA-DR very weakly, at almost baseline levels, but HLA-B27, B2-microglobulin and HLA-DQ were expressed at various levels. After treatment of KATO-3 cells with PSK, the expression of HLA-B27 and beta 2-microglobulin was significantly enhanced. Colo205 cells expressed all class-I antigens tested in this study at different levels, but class-II antigens at almost baseline levels. PSK also enhanced the expression of class-I antigens on Colo205 cells. ICAM-1 was expressed on KATO-3, but not on Colo205. The expression of ICAM-1 was enhanced to a greater extent by treatment with 10 micrograms/ml than with 100 micrograms/ml of PSK. Adenocarcinoma antigen AC-81 was strongly expressed on both cell lines, but PSK-treatment significantly enhanced its expression. These results suggested that enhancement of HLA class-I expression on tumor cells after PSK treatment may be one of the mechanisms responsible for the induction of anti-tumor immunity by PSK.