尾崎 行男

OBJECTIVES:: Pancreatic ductal epithelia contain an abundance of carbonic anhydrase (CA), and the presence of antibodies to this enzyme has been described in autoimmune disorders. We previously found a small amount of an immunoglobulin G-like material in purchased CAII reagents, which led to pseudopositive reactions. METHODS:: We determined the optimum measurement conditions for detecting anti-CAII antibody using an enzyme-linked immunosorbent assay and sera from 140 patients with pancreatic diseases. RESULTS:: Compared with the prevalence of anti-CAII antibody in healthy subjects, a significantly higher seroprevalence of the antibody was detected in patients with autoimmune pancreatitis (AIP) (88.9%, P &lt 0.02), Sjögren syndrome (67.6%, P &lt 0.01), and alcoholic chronic pancreatitis (45.8%, P &lt 0.01). No positive results were obtained among patients with pancreatic cancer. Moreover, the antibody value obtained in the pancreatic cancer patients was actually lower than that obtained in healthy subjects. CONCLUSIONS:: The anti-CAII antibody is probably not a specific marker of AIP because it was present at a higher frequency in the sera of patients with other pancreatic diseases. Nevertheless, the anti-CAII antibody may be a useful tool for the differential diagnosis of AIP and pancreatic cancer. © 2008 by Lippincott Williams &amp Wilkins.

Background: Since sphingosine-1-phosphate (Sph-1-P) plays an important role as an extracellular mediator through interaction with specific cell surface receptors, especially in the area of vascular biology and immunology/haematology, determination of its plasma concentration may become important from the clinical viewpoint. Thus, we attempted to develop a method of measuring the plasma Sph-1-P concentration for use in the clinical laboratory setting. Methods: After two-step lipid extraction, Sph-1-P was coupled with o-phthaldialdehyde, and the resultant fluorescent derivative was separated by high-performance liquid chromatography. C-17-Sph-1-P was used as the internal standard, instead of dihydrosphingosine-1-phosphate, which had been used previously for the same purpose but was actually detected in plasma. Results: Our procedures for preparing the plasma samples and assay Sph-1-P were found to be satisfactory for clinical laboratory testing. The plasma Sph-1-P concentrations were significantly higher in men (413.1 +/- 52.0 nmol/L; mean +/- SD) than in women (352.4 +/- 39.7 nmol/L). Unexpectedly, strong positive correlations were found between the plasma Sph-1-P concentration and red blood cell (RBC)-related parameters, rather than platelet-related parameters. Conclusions: Our present study confirmed the possibility of the clinical introduction of plasma Sph-1-P measurement, and in addition, suggested that RBCs may be involved in the regulation of plasma Sph-1-P concentrations.

Background: Lysophosphatidic acid (LPA) plays important roles in a variety of biological responses, especially in the area of vascular biology, and the determination of its plasma concentration is believed to be important. Several mechanisms are known to be involved in the metabolism of LPA. Methods: To identify factors that may determine the plasma concentrations of this important bioactive lipid, we examined its concentrations using an enzymatic cycling assay and related parameters in 146 healthy subjects. Results: The LPA concentration was significantly higher in women (mean +/- SD, 0.103 +/- 0.032 mu mol/L; n = 47) than in men (0.077 +/- 0.026 mu mol/L; n = 99). A multiple regression analysis showed a strong positive correlation between the plasma LPA concentration and serum lysophospholipase D (lysoPLD) activity, while the LPA concentration was correlated with the plasma lysophosphatidylcholine (LPC) concentration only in men. Other lipid-related parameters were only slightly correlated or were not correlated with the LPA concentration. Conclusions: Our findings suggested that conversion from LPC by lysoPLD might be the major route for LPA production in plasma.

Although the role of collagen in thrombosis has been extensively investigated, the contribution of other extracellular matrices is still unclear. We have recently reported that laminin stimulates platelet spreading through integrin alpha(6)beta(1)-dependent activation of the collagen receptor glycoprotein ( GP) VI under static condition. Under physiological high and low shear conditions, platelets adhered to laminin, and this was strongly inhibited by an antibody that blocks association between GPIb-IX-V and von Willebrand factor (VWF). Moreover, platelets of type III von Willebrand disease or Bernard-Soulier syndrome adhered to laminin at a low shear condition but not at a high shear condition. The specific binding of laminin to VWF was confirmed by surface plasmin resonance spectroscopy (BIAcore). These findings suggest that laminin supports platelet adhesion depending on the interaction of VWF and GPIb-IX-V under pathophysiological high shear flow. This mechanism is similar to that of collagen. We propose that integrins, GPVI, GPIb-IX-V, and VWF represent a general paradigm for the interaction between platelets and subendothelial matrices.

Two major anthocyanins (A1 and A2) were isolated from peels of the spears of Asparagus officinalis cv. Purple Passion. They were purified by column, paper and high-performance liquid chromatographic separations, and their structures were elucidated by high-resolution Fourier transform ion cyclotron resonance mass spectrometry (HR-FT-ICR MS), (1)H, (13)C and two-dimensional NMR spectroscopic analyses and either acid or alkaline hydrolysis, respectively. A1 was identified as cyanidin 3-[3 ''-(O-beta-D-glucopyranosyl)-6 ''-(O-alpha-L-rhamnopyranosyl)-O-beta-D-glucopyranoside], whereas A2 was cyanidin 3-rutinoside, which is widely distributed in higher plants. Oxygen radical absorbance capacity (ORAC) assays proved their high antioxidant activities. (C) 2008 Elsevier Ltd. All rights reserved.

GIT1 is an adaptor protein, which links signaling proteins to focal adhesion, thereby regulating cytoskeletal reorganization. Platelets undergo dynamic cytoskeletal reorganization during platelet activation, for which a large number of adaptor proteins are required. However, there has been no report of GIT1 in platelets. We found that GIT1 was abundantly expressed in platelets and underwent tyrosine phosphorylation downstream of integrin alpha(IIb)beta(3), which was inhibited by the Src kinase inhibitor PP2. Furthermore, GIT1 constitutively associated with beta PIX, a guanine nucleotide exchange factor (GEF) for Rac. The GIT1/beta PIX complex associated with alpha(IIb)beta(3), concomitantly with GIT1 tyrosine phosphorylation. Moreover, both GIT1 and alpha(IIb)beta(3) rapidly translocated to the cytoskeletal fraction during platelet aggregation, which was not observed in the absence of aggregation. These results suggest that tyrosine phosphorylation of GIT1 by Src kinases may regulate cytoskeletal reorganization downstream of alpha(IIb)beta(3) by bringing the Rac GEF beta PIX to the vicinity of the integrin. (c) 2008 Elsevier Inc. All rights reserved.

Appearance of albino seedlings caused by plastome-nuclear genome incompatibility was avoided by using polyploid parents in intersubgeneric hybridization between evergreen azaleas and deciduous Rhododendron japonicum f. flavum. Intra- and interploid crosses of 2x or 4x evergreen azaleas with 2x R. japonicum f. flavum showed high capsule set, but their reciprocal crosses failed to set capsules. Green and albino hybrids were obtained from 2x evergreen azaleas x 2x R. japonicum f. flavum crosses where ptDNAs of the green and albino plants were derived from R. japonicum f. flavum (paternal parent) and evergreen azaleas (maternal parents), respectively. All the progenies from the crosses of 4x evergreen azaleas x 2x R. japonicum f. flavum were green triploids with evergreen azalea-specific ptDNA. The efficiency of obtaining green hybrids in interploid crosses was higher than that in intraploid crosses. These results suggest that interploid crosses of 4x evergreen azaleas x 2x R. japonicum f. flavum can overcome plastome-nuclear genome incompatibility between evergreen azalea-specific plastome and the nuclear genome in the resulting hybrid. (c) 2007 Elsevier B.V. All rights reserved.

An experiment was conducted with a view to find out the possibility of inducing parthenocarpic fruit in teasle gourd (kakrol, Momodrica dioica Roxb.). The experiment was laid out at BSMRAU, Gazipur, Bangladesh during summer season of 2001 and 2002. Seven plant growth regulators (PGR's) viz. auxins (NAA: naphthaleneacetic acid and 2,4-D: 2,4-dichlorophenoxyacetic acid), cytokinins (CPPU: N-(2-chloro-4 pyridyl)-N'phenyl urea, Fulmet: forchlorophenuron), gibberellin (GA(3) : gibberellin A(3)) and auxin transport inhibitors (TIBA: 2, 3, 5-triiodobenzoic acid and MH: maleic hydrazide) with three concentrations (25, 50 and 100 ppm) were sprayed at three times (a day before, at and a day after anthesis) with split-split plot design. Out of seven, only three PGR's (2,4-D, Fulmet and CPPU) were effective to parthenocarpic fruit development. Fruit size and weight increased with increase of concentration of PGRs except 2,4-D. Induced parthenocarpic fruits had no seeds. Control treatments (water spray) produced no fruits. The results revealed the possibility of developing parthenocarpy or seedless fruit using PGR's in teasle gourd.

The mucin-type sialoglycoprotein podoplanin (aggrus) is involved in tumor cell-induced platelet aggregation and tumor metastasis. C-type lectin-like receptor-2 (CLEC-2) was recently identified as an endogenous receptor of podoplanin on platelets. However, the pathophysiological importance and function of CLEC-2 have not been elucidated. Here we clarified the pathophysiological interaction between podoplanin and CLEC-2 in vitro and in vivo. Using several deletion mutants of CLEC-2 expressed as Fc chimeras, we first identified an important podoplanin-recognition domain in CLEC-2. Furthermore, the podoplanin-CLEC-2 interaction was confirmed using several deletion mutants of podoplanin expressed as Fc chimeras. Not only the disialyl-core1-attached glycopeptide but also the stereostructure of the podoplanin protein was found to be critical for the CLEC-2-binding activity of podoplanin. We next synthesized various glycopeptides of podoplanin that included both the platelet aggregation-stimulating domain and O-glycan on Thr52. Interestingly, a disialyl-core1-attached glycopeptide was recognized specifically by CLEC-2. Moreover, the anti-podoplanin monoclonal antibody NZ-1 suppressed both the podoplanin-CLEC-2 interaction and podoplanin-induced pulmonary metastasis, suggesting that CLEC-2 is the first pathophysiological receptor of podoplanin to be identified. In summary, we clarified the molecular interaction in vitro and in vivo between a platelet aggregation-inducing factor, podoplanin, and its specific pathophysiological receptor on platelets, CLEC-2. Podoplanin and CLEC-2 might represent promising therapeutic targets in cancer metastasis.

Platelet aggregometry by the laser light scattering (LS) method is sufficiently sensitive to detect small platelet aggregates that form spontaneously in vitro in the absence of agonists. Platelet aggregation without agonists is named spontaneous platelet aggregation (SPA). Since SPA has been suggested to be associated with various thrombotic diseases, it is essential to measure SPA and to establish a standard range of SPA values. In this study, we measured SPA in 167 healthy subjects by the LS method and attempted to clarify various factors influencing SPA, including the blood collection procedure. We also attempted to establish a tentative standard range of SPA values. SPA was quantitatively measured in terms of the maximum total LS intensity, which reflects small aggregates formed over 10 minutes (SMAX) and the area under the total LS intensity curve of small aggregates (SAUC). Since both the values of SMAX and SAUC were skewed and the log SMAX and log AUC values showed a normal distribution, the statistical analyses were performed using log SMAX and log SAUC. The log SMAX and log SAUC were significantly higher in the samples collected using a tourniquet and/or a 21 G needle, than in those collected without a tourniquet and/or with an 18 G needle. The log SAUC values were significantly lower in samples obtained with a syringe and/or 3.8% sodium citrate than in those obtained in vacuum sampling tubes and/or 3.13% or 3.14% sodium citrate. The Ht and plasma glucose concentration influenced the log SMAX values. We propose that to standardize SPA measurements, the measurements should be completed within two hours of blood sample collection and collected using the regular concentration of citrate. The standard range of SMAX values measured in samples obtained using a tourniquet and a 21 G needle was 2.0-23.99 (*103 mV*count). The standard range of SAUC values measured under same conditions was 0.58-9.12 (*106 mV*count*min). The standard range of SMAX values measured in samples obtained using a tourniquet, 21 G needle and a vacuum tube was 1.7-29.51 (*103 mV*count). The standard range of SAUC values measured under same conditions was 0.59-9.33 (*106 mV*count*min).

Microparticles released from cells (MPs) may play a role in the normal hemostatic response to vascular injury and a rote in clinical diseases because they express phospholipids, which function as procoagulants. Although flow cytometry is the most widely used method for studying MPs, some novel assays such as tissue factor-dependent procoagulant assay or the ELISA mothod have been reported. However, the use of MP quantification as a clinical toot is still a matter of debate. Elevated platelet-derived MP, endothelial celt-derived MP, and monocyte-derived MP concentrations are documented in almost all thrombotic diseases occurring in both venous and arterial beds. However, the clear significance of MPs in various clinical conditions remains controversial. For example, it is not known if MPs found in peripheral blood vessels cause thrombosis, or whether they are the result of thrombosis. On the other hand, numerous studies have shown that not only the quantity but also the cellular origin and composition of circulating MPs are dependent on the type of disease, the disease state and medical treatment. In addition, many different functions have also been attributed to MPs. Thus, the number and type of clinical disorders associated with elevated MPs is currently increasing. (C) 2008 Elsevier Ltd. All rights reserved.

We examined photoperiodic response of lotus (Nelumbo nucifera) rhizome morphogenesis (its transition to a storage organ) by using seed-derived plants. Rhizome enlargement (increase in girth) was brought about under 8, 10 and 12 h photoperiods, whereas the rhizomes elongated under 13 and 14 h photoperiods. Rhizomes elongated under 14 h light regimes supplied as 8 h of natural light plus 6 h supplemental hours of white, yellow or red light, but similar treatments with supplemental blue, green or far red light, caused enlargement in girth of the rhizomes. A 2 h interruption of the night with white, yellow or red light, in plants entrained to 8 h photoperiod brought rhizome elongation, whereas 2 h-blue, green or far red light night breaks still resulted in rhizome increase in girth. The inhibitory effect of a red (R) light night break on rhizome increase in girth was reversed by a far-red (FR) light given immediately afterwards. Irradiation with R/FR/R inhibited the rhizome increase in girth. FR light irradiation following R/FR/R irradiation cancelled the effect of the last R light irradiation. It was demonstrated that the critical photoperiod for rhizome transition to storage organ is between 12 and 13 h photoperiod. It was also evident that the optimal light quality range for interruption of dark period (night break) is between yellow and red light and that a R/FR reversible reaction is observed. From these results, we propose that phytochrome plays an important role in photoperiodic response of rhizome increase in girth in lotus. This is the first report on phytochrome-dependent morphogenesis of storage organs in rhizomous plants.

Podoplanin ( aggrus), a transmembrane sialoglycoprotein, is involved in tumor cell-induced platelet aggregation, tumor metastasis, and lymphatic vessel formation. However, the mechanism by which podoplanin induces these cellular processes including its receptor has not been elucidated to date. Podoplanin induced platelet aggregation with a long lag phase, which is dependent upon Src and phospholipase C gamma 2 activation. However, it does not bind to glycoprotein VI. This mode of platelet activation was reminiscent of the snake toxin rhodocytin, the receptor of which has been identified by us as a novel platelet activation receptor, C-type lectin-like receptor 2 ( CLEC-2) ( Suzuki-Inoue, K., Fuller, G. L., Garcia, A., Eble, J. A., Pohlmann, S., Inoue, O., Gartner, T. K., Hughan, S. C., Pearce, A. C., Laing, G. D., Theakston, R. D., Schweighoffer, E., Zitzmann, N., Morita, T., Tybulewicz, V. L., Ozaki, Y., and Watson, S. P. ( 2006) Blood 107, 542-549). Therefore, we sought to evaluate whether CLEC-2 serves as a physiological counterpart for podoplanin. Association between CLEC-2 and podoplanin was confirmed by flow cytometry. Furthermore, their association was dependent on sialic acid on O-glycans of podoplanin. Recombinant CLEC-2 inhibited platelet aggregation induced by podoplanin-expressing tumor cells or lymphatic endothelial cells, suggesting that CLEC-2 is responsible for platelet aggregation induced by endo-genously expressed podoplanin on the cell surfaces. These findings suggest that CLEC-2 is a physiological target protein of podoplanin and imply that it is involved in podoplanin-induced platelet aggregation, tumor metastasis, and other cellular responses related to podoplanin.

Platelet-derived mediators may play an important role in the development of renal diseases through interaction with glomerular mesangial cells (MCs), and we, in this study, examined the effect of sphingosine 1-phosphate (Sph-1-P), a bioactive lipid released from activated platelets, on the contraction of MCs. Sph-1-P was found to induce MC contraction through mediation of Rho kinase both in cell shape change and collagen gel contraction assays. The specific antagonist of the Sph-1-P receptor S1P(2) inhibited the response. Similar results were obtained when the supernatant from activated platelet suspensions were used instead of Sph-1-P. Our findings suggest that platelet-derived Sph-1-P may be involved in MC contraction via S1P(2) and that regulation of this receptor might be useful therapeutically.

Fluid shear stress modulates the functional responses of platelets and vascular cells, and plays an important role in the pathogenesis of vascular disorders, including atherosclerosis and restenosis. Since shear stress induces activation of platelets, which abundantly store sphingosine 1-phosphate (Sph-1-P), and upregulates the mRNA expression of S1P(1), the most important Sph-1-P receptor expressed on the endothelial cells, we examined the effects of shear stress on the Sph-1-P-related responses involving these cells. Shear stress was found to induce Sph-1-P release from the platelets in a shear intensity- and time-dependent manner. Inhibitors of protein kinase C suppressed this mechanical force-induced Sph-1-P release, suggesting involvement of this kinase. On the other hand, in vascular endothelial cells, shear stress increased SIP, protein expression, as revealed by flow-eytometric analysis, and the responsiveness to Sph-1-P, which was assessed by monitoring the intracellular Ca2+ concentration. These results indicate that shear stress enhances the Sph-1-P responses in cell-cell interactions between platelets and endothelial cells. (C) 2007 Elsevier Inc. All rights reserved.

The two lectin receptors, CLEC-2 and Dectin-1, have been shown to signal through a Syk-dependent pathway, despite the presence of only a single YXXL in their cytosolic tails. In this study, we show that stimulation of CLEC-2 in platelets and in two mutant cell lines is dependent on the YXXL motif and on proteins that participate in signaling by immunoreceptor tyrosine-based activation motif receptors, including Src, Syk, and Tec family kinases, and on phospholipase C gamma. Strikingly, mutation of either Src homology (SH) 2 domain of Syk blocks signaling by CLEC-2 despite the fact that it has only a single YXXL motif. Furthermore, signaling by CLEC-2 is only partially dependent on the BLNK/ SLP-76 family of adapter proteins in contrast to that of immunoreceptor tyrosinebased activation motif receptors. The C-type lectin receptor, Dectin-1, which contains a YXXL motif preceded by the same four amino acids as for CLEC-2 ( DEDG), signals like CLEC-2 and also requires the two SH2 domains of Syk and is only partially dependent on the BLNK/SLP-76 family of adapters. In marked contrast, the C-type lectin receptor, DCSIGN, which has a distinct series of amino acids preceding a single YXXL, signals independent of this motif. A mutational analysis of the DEDG sequence of CLEC-2 revealed that the glycine residue directly upstream of the YXXL tyrosine is important for CLEC-2 signaling. These results demonstrate that CLEC-2 and Dectin-1 signal through a single YXXL motif that requires the tandem SH2 domains of Syk but is only partially dependent on the SLP- 76/ BLNK family of adapters.

Maternal inheritance of chloroplast DNA (cpDNA) in the genus Camellia was confirmed using the polymorphism of atpH-atpI region. CpDNAs of all C. X vernalis cultivars showed the same type as those of C. sasanqua, and all the progenies from C. X vernalis, either open pollinated or crossed, had the same cpDNA type as their maternal plants. Flow cytometry subjected to estimate the ploidy level of C. japonica, C. sasanqua and C. X vernalis revealed that there is a very strong positive linear correlation (r(2)=0.981) between fluorescent intensity and ploidy level, Suggesting that the method is useful to investigate the ploidy level in Camellia. Natural occurrence of ploidy variation was shown in the progenies of tetraploid C. X vernalis cultivars, and zygote patterns of the progenies are discussed.

We examined the response of rhizome growth to red light. break under different short daylengths in lotus (Nelumbo nucifera) seedlings. Maximum inhibitory response of rhizome enlargement to light-break under 10, 8 and 4hr daylengths occurred 10, 8-10 and 12-14hrs after the beginning of the dark period, respectively. It was found that rhythmic response to light break is involved in rhizome growth of lotus.

The ongoing trend toward downsizing and the growing sophistication of electronic devices require increasingly higher LSI mounting densities. Flip-chip technology is used to mount LSIs without using wire and thus enables higher mounting densities than conventional mounting technology, which uses Au wire bonding. Fujitsu has developed a new high-density flip-chip mounting technology for use in consumer products to reduce size and improve performance. This paper describes the bump method, assembly process, reliability, and applications of this new technology. It also examines Fujitsu's efforts to develop an ultrasonic assembly technology that achieves high throughput and reduced cost.

The integrin U-IIb beta(3) plays a critical role in mediating clot retraction by platelets which is important in vivo in consolidating thrombus formation. Actin-myosin interaction is essential for clot retraction. In the present study, we demonstrate that the structurally distinct Src kinase inhibitors, PP2 and PD173952, significantly reduced the rate of clot retraction, but did not prevent it reaching completion. This effect was accompanied by abolition Of alpha(IIb)beta(3)-dependent protein tyrosine phosphorylation, including PLC-gamma 2. A role for PLC-gamma 2 in mediating clot retraction was demonstrated using PLC-gamma 2-deficient murine platelets. Furthermore, platelet adhesion to fibrinogen leads to MLC phosphorylation through a pathway that is inhibited by PP2 and by the PLC inhibitor, U73122. These results demonstrate a partial rote for Src kinase-dependent activation of PLC-gamma 2 and MLC phosphorylation in mediating clot retraction downstream of integrin alpha(IIb)beta(3). (C) 2006 Elsevier Ltd. All rights reserved.

Background and Purpose: It is widely accepted that antiplatelet therapy is effective for secondary prevention of atherosclerotic vascular diseases. We performed a double-blind, controlled clinical-pharmacological study to investigate the antiplatelet efficacy of sarpogrelate, a selective 5-hydroxy-tryptamine (5-HT2A) receptor antagonist, in patients with ischemic stroke, using a new assessment system employing combinations of 5-HT and epinephrine as agonists. Methods: Forty-seven patients with ischemic stroke were randomly assigned to three groups: 15 patients received 25 mg sarpogrelate (group L), 16 patients received 50 mg (group M), and 15 patients received 100 mg (group H) orally, three times daily for 7 days. The effect was expressed as maximum intensity of platelet aggregation on the last day of medication. Two combinations of agonists, 0.5 mu mol/l 5-HT plus 3 mu mol/l epinephrine, and 1 mu mol/l 5-HT plus 3 mu mol/l epinephrine, were used to induce platelet aggregation. Results: With both combinations of agonists, sarpogrelate treatment inhibited platelet aggregation dose-dependently (p < 0.025, Jonckheere test). In multiple-group comparison, the effect in group H was greater than that in group L or M (p < 0.025, Wilcoxon rank-sum test). Conclusion: Sarpogrelate treatment inhibited platelet aggregation dose-dependently in patients with ischemic stroke, as judged by a new assessment system employing combinations of 5-HT and epinephrine as agonists. Copyright (c) 2007 S. Karger AG, Basel.

The genotype of hepatitis C virus (HCV) and the amount of HCV RNA are often used to predict the efficacy of interferon (IFN) therapy on chronic hepatitis C. In addition to these factors, there may be several factors related to the host. Therefore, the authors undertook a retrospective study in which physical findings and laboratory data before therapy were evaluated by multiple logistic analysis. Two-hundred and five cases with chronic hepatitis C treated with interferon were analyzed in this study. Sustained virological response was observed with 68 cases. Multiple logistic analysis-was performed with 29 explanatory variables including HCV genotype, HCV RNA, IFN types, and total dose, along with gender, age, alcohol consumption, body mass index (BMI), histological findings of liver biopsy, platelet counts, and laboratory data of serum enzymes. Analysis on the factors that correlated well with therapeutic efficacy revealed that genotype 2a, 2b showed higher therapeutic responses than genotype 1b with reference to HCV genotypes, and higher IFN dose or lower HCV RNA levels gave better results. With reference to host factors, higher total protein level, lower levels of BMI, total bilirubin, and aspartate aminotransferase were highly correlated with therapeutic efficacy. HCV genotypes and HCV RNA levels have been already identified as prognostic factors. However, the high correlation values of BMI and the total protein level are new findings. It is suggested that probability estimation of therapeutic effects using the logistic regression equation may be a good tool for predicting therapeutic efficacy of IFN therapy on individual cases.