Biomedical subjects

S Watanabe

Publications and source records attributed to S Watanabe.

At least 19 recordsLinked to original sources

PubMed2006

Beneficial effect of interferon-beta treatment in patients with multiple sclerosis is associated with transient increase in serum IL-6 level in response to interferon-beta injection.

In order to predict the clinical benefit of interferon-beta (IFN-beta) to patients with multiple sclerosis (MS), the following markers were investigated; (1) chronological change of cytokines (IFN-gamma, TNF-alpha, IL-6, IL-10, and TGF-beta) after administration of IFN-beta, (2) untoward effects of IFN-beta such as headache and arthralgia, (3) backgrounds of the patients such as age and relapse rate, (4) efficacy of IFN-beta therapy assessed by the change of relapse rate and progression of disability. Chronological blood sampling was performed 0, 10, and 24 h after injection of IFN-beta. The increase of serum IL-6 level in response to IFN-beta administration was associated with headache, arthralgia, relapse rate before treatment, and disability score at the initiation of the therapy. Significant association of change of serum TNF-alpha with age and headache was also observed. The important finding in this study was that patients with a transient increase in IL-6 in response to IFN-beta showed a slow disease progression. This result suggests that this transient increase in the serum IL-6 predicts favorable response to IFN-beta treatment.

Adult↗

PubMed2006

Mobile phone use and acoustic neuroma risk in Japan.

OBJECTIVES: The rapid increase of mobile phone use has increased public concern about its possible health effects in Japan, where the mobile phone system is unique in the characteristics of its signal transmission. To examine the relation between mobile phone use and acoustic neuroma, a case-control study was initiated. METHODS: The study followed the common, core protocol of the international collaborative study, INTERPHONE. A prospective case recruitment was done in Japan for 2000-04. One hundred and one acoustic neuroma cases, who were 30-69 years of age and resided in the Tokyo area, and 339 age, sex, and residency matched controls were interviewed using a common computer assisted personal interview system. Education and marital status adjusted odds ratio was calculated with a conditional logistic regression analysis. RESULTS: Fifty one cases (52.6%) and 192 controls (58.2%) were regular mobile phone users on the reference date, which was set as one year before the diagnosis, and no significant increase of acoustic neuroma risk was observed, with the odds ratio (OR) being 0.73 (95% CI 0.43 to 1.23). No exposure related increase in the risk of acoustic neuroma was observed when the cumulative length of use (<4 years, 4-8 years, >8 years) or cumulative call time (<300 hours, 300-900 hours, >900 hours) was used as an exposure index. The OR was 1.09 (95% CI 0.58 to 2.06) when the reference date was set as five years before the diagnosis. Further, laterality of mobile phone use was not associated with tumours. CONCLUSIONS: These results suggest that there is no significant increase in the risk of acoustic neuroma in association with mobile phone use in Japan.

Adult↗

PubMed2006

The effect of Pseudomonas aeruginosa on pulmonary function in patients with bronchiectasis.

Bronchiectasis patients are susceptible to infection with Pseudomonas aeruginosa. Isolation is associated with increased severity of disease, greater airflow obstruction and poorer quality of life. It is not known whether infection by P. aeruginosa is a marker of disease severity or contributes to disease progression. Consecutive non-cystic fibrosis adult bronchiectasis outpatients (n = 163) with multiple sputum cultures and follow-up pulmonary function tests were designated, according to isolation of P. aeruginosa, as "never infected" (group 1; n = 67), "intermittently isolated" (group 2; n = 82) and "chronically infected" (group 3; n = 14). Based upon change in forced expiratory volume in one second (FEV(1)) % predicted levels at >or=2 yrs after presentation, longitudinal behaviour was characterised as "improvement" (>or=10% rise), "decline" (>or=10% fall) or "stability". Baseline pulmonary-function tests and longitudinal behaviour were examined in relation to pseudomonas status. There was no difference between the groups in age, sex, smoking habit or length of follow-up. Baseline FEV(1) levels were highest in group 1 (mean+/-sd: 77.4+/-24.3) and higher in group 2 (67.3+/-25.7) than in group 3 (55.2+/-18.5). The same significant trends were seen for baseline FEV(1)/forced vital capacity ratios and diffusing capacity of the lung for carbon monoxide levels. Subsequent longitudinal behaviour was linked to baseline FEV(1) levels, which were lowest in patients with improvement and lower in association with decline than with stability. However, longitudinal behaviour did not differ between groups 1, 2 and 3, either before or after adjustment for baseline FEV(1) levels. Infection by Pseudomonas aeruginosa occurs in bronchiectasis patients with more severe impairment of pulmonary function but does not influence rate of decline in pulmonary function either before or after adjustment for baseline disease severity. Thus, Pseudomonas aeruginosa is a marker of bronchiectasis severity but is not linked to an accelerated decline in pulmonary function.

Adult↗

PubMed2006

Iatrogenic amyloid neuropathy in a Japanese patient after sequential liver transplantation.

A 57-year-old woman in Japan, the first recipient of part of a liver from a 58-year-old man with familial amyloidotic polyneuropathy (FAP) amyloidogenic transthyretin Val30Met who had had sensorimotor polyneuropathy in the lower limbs for 3 years, started to develop sensory neuropathy 7 years after transplantation. Before the July 1998 sequential transplantation, she had been in a hepatic coma at the terminal stage of primary biliary cirrhosis and waiting for deceased donor liver transplantation. In September 2004, biopsy samples of her duodenum first showed amyloid deposition. Although biopsy materials in 2005 and 2006 showed no changes in amyloid deposition, decreased temperature sensation and pain in fingertips and toes were detected at a neurologic examination in March 2006. Thus, clinical symptoms of FAP appeared about 2 years after amyloid deposition started. Nerve conduction velocity studies revealed mild to moderate axonal sensory polyneuropathy without demyelination. Our findings confirmed iatrogenic sensory neuropathy induced by amyloid deposition 7 years after sequential liver transplantation.

Amyloid Neuropathies, Familial↗

PubMed2006

Vitamin D and intact PTH status in patients with hip fracture.

INTRODUCTION: The prevalence of hypovitaminosis D in patients with acute hip fracture was examined in a population on Sado Island in Japan. There were 85 cases of hip fracture among this population in 2004, giving an overall incidence of hip fracture of 121.4 per 100,000 population per year. This study included 50 of the 85 cases, and these cases were defined as the hip fracture group. Patients older than 70 years without established osteoporosis who were admitted to the hospital on the island during almost the same period for treatment of an orthopedic condition other than a hip fracture were defined as the control group. MATERIALS AND METHODS: The levels of serum 25-hydroxyvitamin D (25-OHD), intact parathyroid hormone (intact PTH), alkaline phosphatase (ALP), albumin, and the number of remaining teeth were examined in each group. In the hip fracture group, serum calcium, serum phosphorus, urine N-terminal cross-linking telopeptide of type I collagen (NTx), bone mineral density (BMD) of the nonfractured hip, the presence of a vertebral fracture on X-ray, severity of dementia, and physical activity level were also examined. RESULTS: Both the serum 25-OHD and serum albumin levels were significantly lower in patients with hip fracture than in controls, and the intact PTH level was significantly higher in patients with hip fracture. The number of remaining teeth was correlated with age, and was also significantly correlated with 25-OHD. In the hip fracture group, 62% of the subjects had hypovitaminosis D (25-OHD <20 ng/ml) and one-fifth of cases with hypovitaminosis D showed elevated PTH levels (>65 pg/ml). On the other hand, in the control group, hypovitaminosis D occurred in 18.9% of the subjects, and only one case showed elevated PTH. The serum 25-OHD level showed a decrease as the severity of dementia progressed and the activity level decreased. CONCLUSION: Our results indicate that about two-thirds (62%) of hip fracture patients had vitamin D insufficiency, suggesting that this condition may be closely associated with hip fracture in elderly people. Therefore, the serum 25-OHD level may be a useful index for the risk of hip fracture in elderly people.

Aged↗

PubMed2006

Acceleration of de novo cholesterol synthesis in the epidermis influences desquamation of the stratum corneum in aged mice.

Cholesterol, a component of intercellular lipids, is important for stratum corneum (SC) homeostasis, including its barrier function and desquamation. However, cholesterologenesis in the epidermis decreases under basal conditions with aging. We found that the number of horny layers in murine SC increased with the decrease of desquamation in the outermost corneocytes associated with aging. The cholesterol content decreased and the cholesterol sulfate content increased in the horny layer with aging, which resulted in an increase in the ratio of cholesterol sulfate to cholesterol. Moreover, we investigated the effects of accelerated cholesterologenesis on desquamation in aged murine skin following topical application of mevalonic acid. The ratio of cholesterol sulfate to cholesterol in aged murine SC significantly decreased following topical treatment with mevalonic acid, which resulted from an increase in cholesterol content via the acceleration of cholesterologenesis. Treatment with mevalonic acid also significantly reduced the number of cell layers in the SC along with the acceleration of desquamation, as measured by desmoglein I content, corneocyte surface area and proteinase activity. These results indicate that an improvement in the ratio of cholesterol sulfate to cholesterol content by de novo cholesterologenesis may be important for desquamation of the SC in aged epidermis.

Aging↗

PubMed2006

Seasonal variations in 228Ra/226Ra ratio within coastal waters of the Sea of Japan: implications for water circulation patterns in coastal areas.

In this study, low-background gamma-spectrometry was used to determine the (228)Ra/(226)Ra ratio of 131 coastal water samples from various environments around Honshu Island, Japan (mainly around Noto Peninsula) at 1-3 month intervals from April 2003 until September 2005. Spatial variation in (228)Ra/(226)Ra ratios was also assessed by analyzing 34 coastal water samples from five areas within the Sea of Japan during May and June 2004. The (228)Ra/(226)Ra ratio of coastal water from all sites around Noto Peninsula shows seasonal variation, with minimum values during summer ((228)Ra/(226)Ra=0.7) and maximum values during autumn-winter ((228)Ra/(226)Ra=1.7-2). This seasonal variation is similar to that recorded for coastal water between Tsushima Strait and Noto Peninsula. The measured lateral variation in (228)Ra/(226)Ra ratios within coastal water between Tsushima Strait and Noto Peninsula is only minor (0.5-0.7; May-June 2004). Coastal waters from two other sites (Pacific shore and Tsugaru Strait, north Honshu) show no clear seasonal variation in (228)Ra/(226)Ra ratio. These measured variations in (228)Ra/(226)Ra ratio, especially the temporal variations, have important implications for seasonal changes in patterns of coastal water circulation within the Sea of Japan.

Environmental Monitoring↗

PubMed2006

Human blood monitoring program in Japan: contamination and bioaccumulation of persistent organochlorines in Japanese residents.

Concentrations of persistent organochlorines (OCs)-such as polychlorinated biphenyls (PCBs), 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and its metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), chlordane compounds (CHLs), hexachlorobenzene, and tris(4-chlorophenyl)methane [TCPMe]-were determined in plasma samples from residents of three sub-metropolitan locations in Japan (Miyako, Saku, and Tottori) for the purpose of studying the geographic variation and specific accumulation of OCs. Residue concentrations of PCBs and DDTs were the highest in samples collected in Saku (400 and 370 ng/g lipid wt, respectively) whereas samples from Miyako contained greater CHL residues (70 ng/g lipid wt) than those from the other two locations. This contamination pattern reflects the historic use of OCs in each area. For the first time, tris (4-chlorophenyl) methane (TCPMe) concentrations were detected in most of the plasma sample analyzed. Concentrations of TCPMe which ranged from <0.1 to 8.1 ng/g lipid wt eight, were lower than those previouly reported in other human tissue. Larger geographic differences in OC accumulation were observed for PCBs and CHLs, whereas DDTs and HCHs exhibited little variability. PCB concentrations in samples from Saku residents were higher than those from residents of countries in the circumpolar Arctic region but lower than those reported for some populations in the United States and Western European countries. Interestingly, CHL residue concentrations in human blood from Japan are among the highest values reported for the countries examined, suggesting continued increased exposure to CHLs of the Japanese population. Time-trend analysis of CHLs in human blood samples from Miyako (Okinawa prefecture) showed that CHL residues have decreased substantially during the last decade, indicating the effect of the official ban of CHLs in 1986 in Japan. Isomer-specific analysis of PCBs revealed lower proportions of higher chlorinated congeners such as hepta- and octachlorobiphenyls in women than in men, suggesting the possibility of preferential elimination of higher chlorinated biphenyls in women. The difference in sex-dependent accumulation of OC compounds in healthy and ill persons was suggested. To our knowledge, this is the first report on the specific accumulation of persistent QCs, including TCPMe, in human blood samples from Japan.

Adult↗

PubMed2006

Activation of Akt signaling is sufficient to maintain pluripotency in mouse and primate embryonic stem cells.

Embryonic stem (ES) cells can self-renew indefinitely without losing their differentiation ability to any cell types. Phosphoinositide-3 kinase (PI3K)/Akt signaling plays a pivotal role in various stem cell systems, including the formation of embryonic germ (EG) cells from primordial germ cells and self-renewal of neural stem cells. Here, we show that myristoylated, active form of Akt (myr-Akt) maintained the undifferentiated phenotypes in mouse ES cells without the addition of leukemia inhibitory factor (LIF). The effects of myr-Akt were reversible, because LIF dependence and pluripotent differentiation activity were restored by the deletion of myr-Akt. In addition, myr-Akt-Mer fusion protein, whose enzymatic activity is controlled by 4-hydroxy-tamoxifen, also maintained the pluripotency of not only mouse but also cynomolgus monkey ES cells. These results clearly demonstrate that Akt signaling sufficiently maintains pluripotency in mouse and primate ES cells, and support the notion that PI3K/Akt signaling axis regulates 'stemness' in a broad spectrum of stem cell systems.

Animals↗

PubMed2006

Clinical and MRI features of Japanese patients with multiple sclerosis positive for NMO-IgG.

This study investigates the relation between the serological status of NMO (neuromyelitis optica)-IgG and the clinical and MRI features in Japanese patients with multiple sclerosis. Serum NMO-IgG was tested in 35 Japanese patients diagnosed with multiple sclerosis, including 19 with the optic-spinal form of multiple sclerosis (OSMS), three with the spinal form of multiple sclerosis (SMS), and 13 with the conventional form of multiple sclerosis (CMS), which affects the brain. NMO-IgG was detected in 14 patients, 12 with OSMS and 2 with CMS. In these patients, longitudinally extensive (> 3 vertebral segments) spinal cord lesions (93% v 57%) and permanent, complete blindness (no perception of light) in at least one eye (50% v 0%) were the noticeable features as compared with NMO-IgG-negative OSMS. The two patients having CMS with NMO-IgG had unusual brain lesions, but in other respects had features suggesting OSMS. NMO-IgG was detected in more than half the number of patients with OSMS and in some patients with CMS. This newly discovered serum autoantibody was markedly associated with longitudinally extensive spinal cord lesions and with complete blindness, suggesting severe optic-spinal disease.

Adult↗

PubMed2006

Bulk- and surface-sensitive high-resolution photoemission study of two mott-hubbard systems: SrVO3 and CaVO3.

We study the electronic structure of Mott-Hubbard systems SrVO3 and CaVO3 with bulk and surface-sensitive high-resolution photoemission spectroscopy, using a vacuum ultraviolet laser, synchrotron radiation, and a discharge lamp (hv = 7-21 eV). A systematic suppression of the density of states (DOS) within approximately 0.2 eV of the Fermi level (EF) is found on decreasing photon energy, i.e., on increasing bulk sensitivity. The coherent band in SrVO3 and CaVO3 is shown to consist of surface and bulk-derived features, separated in energy. The stronger distortion on surface of CaVO3 compared to SrVO3 leads to a higher surface metallicity in the coherent DOS at EF, consistent with recent theory.

Journal Article↗

PubMed2006

Heavy-fermion-like state in a transition metal oxide LiV2O4 single crystal: indication of Kondo resonance in the photoemission spectrum.

We have performed a vacuum ultraviolet laser excited photoemission spectroscopy on a d-electron heavy-fermion-like material LiV2O4 single crystal. We observed a sharp peak structure in the density of states at approximately 4 meV above the Fermi level (E(F)). The evolution of the peak height corresponds well with the crossover behavior to the heavy-fermion-like state as observed in the thermal and transport properties. The position, shape, and temperature (T) dependence of the peak structure is quite similar to the Kondo resonance observed in conventional f-electron heavy Fermion compounds.

Journal Article↗

PubMed2006

Effusion and solid lymphomas have distinctive gene and protein expression profiles in an animal model of primary effusion lymphoma.

Lymphoma usually forms solid tumours in patients, and high expression levels of adhesion molecules are observed in these tumours. However, Kaposi's sarcoma-associated herpesvirus (KSHV)-related primary effusion lymphoma (PEL) does not form solid tumours and adhesion molecule expression is suppressed in the cells. Inoculation of a KSHV-associated PEL cell line into the peritoneal cavity of severe combined immunodeficiency mice resulted in the formation of effusion and solid lymphomas in the peritoneal cavity. Proteomics using two-dimensional difference gel electrophoresis and DNA microarray analyses identified 14 proteins and 105 genes, respectively, whose expression differed significantly between effusion and solid lymphomas. Five genes were identified as having similar expression profiles to that of lymphocyte function-associated antigen 1, an important adhesion molecule in leukocytes. Among these, coronin 1A, an actin-binding protein, was identified as a molecule showing high expression in solid lymphoma by both DNA microarray and proteomics analyses. Western and northern blotting showed that coronin 1A was predominantly expressed in solid lymphomas. Moreover, KSHV-encoded lytic proteins, including viral interleukin-6, were highly expressed in effusion lymphoma compared with solid lymphoma. These data demonstrate that effusion and solid lymphomas possess distinctive gene and protein expression profiles in our mouse model, and suggest that differences in gene and protein expression between effusion and solid lymphomas may be associated with the formation of effusion lymphoma or invasive features of solid lymphoma. Furthermore, the results obtained using this combination of proteomics and DNA microarray analyses indicate that protein synthesis partly reflects, but does not correlate strictly with, mRNA production.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Development of diffusion-weighted image using a 0.3T open MRI.

The purpose of this study was to develop a new technique for diffusion-weighted MRI (DWI) with a low-field scanner. DWI is becoming important for assessment of acute stroke. Until recently DWI required expensive technology. We developed multishot-DWI sequence for 0.3T open type MR imager. We prospectively studied forty patients on this 0.3T MRI and compared this DWI to single-shot-DWI by 1.5T-MRI. Group A: Twenty-four patients with acute cerebral infarctions detected by 1.5T-DWI were re-examined using 0.3T-DWI within 24 hours. Sixteen patients with acute cerebral infarctions detected by 0.3T-DWI were re-examined using 1.5T-DWI within 24 hours. In 22 (92%) of 24 cases, 0.3T-DWI showed high signal. In the other two patients, motion artifact distorted 0.3T-DWI. Group B: In all 16 patients, all infarctions detected by 0.3T-DWI showed high signal on 1.5T-DWI. These preliminary data show that, as long as the patient is able to keep still, multishot-DWI can be acquired successfully on a 0.3T open type MRI system.

Aged↗

PubMed2006

Physical association of the patient-specific GATA1 mutants with RUNX1 in acute megakaryoblastic leukemia accompanying Down syndrome.

Mutations of the GATA1 gene on chromosome X have been found in almost all cases of transient myeloproliferative disorder and acute megakaryoblastic leukemia (AMKL) accompanying Down syndrome (DS). Although most GATA1 mutations lead to the expression of GATA1s lacking the N-terminal activation domain, we recently found two novel GATA1 proteins with defects in another N-terminal region. It has been suggested that loss of the N-terminal portion of GATA1 might interfere with physiological interactions with the critical megakaryocytic transcription factor RUNX1, and this would imply that GATA1s is not able to interact properly with RUNX1. However, the interaction domain of GATA1 remains controversial. In this study, we show that GATA1 binds to RUNX1 through its zinc-finger domains, and that the C-finger is indispensable for synergy with RUNX1. All of the patient-specific GATA1 mutants interacted efficiently with RUNX1 and retained their ability to act synergistically with RUNX1 on the megakaryocytic GP1balpha promoter, whereas the levels of transcriptional activities were diverse among the mutants. Thus, our data indicate that physical interaction and synergy between GATA1 and RUNX1 are retained in DS-AMKL, although it is still possible that increased RUNX1 activity plays a role in the development of leukemia in DS.

Animals↗

PubMed2006

Synthetic double-stranded RNA induces multiple genes related to inflammation through Toll-like receptor 3 depending on NF-kappaB and/or IRF-3 in airway epithelial cells.

BACKGROUND: We hypothesized that synthetic double-stranded (ds)RNA may mimic viral infection and induce expression of genes related to inflammation in airway epithelial cells. OBJECTIVE: We analysed what gene was up-regulated by synthetic dsRNA poly I : C and then focused this study on the role of Toll-like receptor 3 (TLR3), a receptor of dsRNA and its transcriptional pathway. METHODS: Airway epithelial cell BEAS-2B and normal human bronchial epithelial cells were cultured in vitro. Expression of targets RNA and protein were analysed by PCR and ELISA. Localization of TLR3 expression in the cells was analysed with flow cytometry. To analyse the role of TLR3 and transcription factors, knockdown of these genes was performed with short interfering RNA (siRNA). RESULTS: Real-time PCR revealed that poly I : C significantly increased the expression of mRNAs for chemokines IP-10, RANTES, LARC, MIP-1alpha, IL-8, GRO-alpha and ENA-78 and cytokines IL-1beta, GM-CSF, IL-6 and the cell adhesion molecule ICAM-1 in both cell types. Increases in protein levels were also observed. Expression of these genes was significantly inhibited in BEAS-2B cells in which TLR3 expression was knocked down. However, pre-treatment with anti-TLR3 mAb, which interferes with the function of TLR3 expressed on the cell surface, did not inhibit the genes expression and these data were concordant with the results that TLR3 was expressed inside airway epithelial cells. The study of siRNA for NF-kappaB and IRF3 showed that they transduce the signal of poly I : C, but their roles were different in each target gene. CONCLUSION: TLR3 is expressed inside airway epithelial cells and transduces synthetic dsRNA signals. These signals may increase expression of inflammatory cytokines, chemokines and ICAM-1 through activation of transcription factors NF-kappaB and/or IRF3 in airway epithelial cells.

Antibodies, Monoclonal↗

PubMed2006

Green tea polyphenol (-)-epigallocatechin-3-gallate inhibits ethanol-induced activation of pancreatic stellate cells.

BACKGROUND: Activated pancreatic stellate cells (PSCs) play a central role in the pathogenesis of pancreatic fibrogenesis and inflammation. Ethanol, a major cause of chronic pancreatitis, directly induces PSC activation and oxidative stress. Inhibition of PSC activation or stimulation to PSC might be an effective therapeutic strategy for the prevention of pancreatic fibrosis, and (-)-epigallocatechin-3-gallate (EGCG), a major component of green tea extracts, is a potent antioxidant of polyphenols. Therefore, we examined the mechanisms through which ethanol induces oxidative stress on PSCs and evaluated the effect of EGCG on activation and cell functions of ethanol-stimulated PSCs. MATERIALS AND METHODS: The PSCs were isolated from the pancreas of male Wister rats with Nycodenz gradient methods and cells between passages one and four were used. Isolated PSCs were cultured with ethanol (50 mM) in the absence or presence of EGCG (5 microM or 25 microM). RESULTS: The EGCG pre-treatment abolished ethanol-induced lipid peroxidation of the cell membrane, loss of total superoxide dismutase (SOD) activity and suppressed ethanol-induced gene expressions of Mn- and Cu/Zn-SOD. EGCG also suppressed ethanol-induced p38 mitogen-activated protein (MAP) kinase phosphorylation, alpha-smooth muscle actin production in PSCs and activated transforming growth factor-beta1 secretion into the medium. Furthermore, EGCG inhibited ethanol-induced type-I procollagen production and collagen secretion. In addition, EGCG inhibited transformation of freshly isolated cells to activated myofibroblast-like phenotype. CONCLUSIONS: Our results suggest that green tea and polyphenols could prevent pancreatic fibrosis by inhibiting PSC activation through the antioxidative effect.

Actins↗

PubMed2006

Hepatitis C virus free-virion and immune-complex dynamics during interferon therapy with and without ribavirin in genotype-1b chronic hepatitis C patients.

The Synergistic effect of interferon (IFN) and ribavirin for patients with chronic hepatitis C has been demonstrated, but ribavirin has no apparent direct antiviral effect against hepatitis C virus (HCV) when used as monotherapy. To elucidate the mechanism of ribavirin on enhanced HCV eradication when used in combination therapy, we investigated the serum HCV dynamics of free-virions (FV) and immune-complexes (IC) in genotype-1b infected patients treated with IFN-alpha2b alone (n = 11) or in combination with ribavirin (n = 15). Serum FV- and IC-HCV RNA were separated by immunoprecipitation using anti-human immunoglobulin and quantified serially using real-time detection polymerase chain reaction. At the first phase (day 0-2), the decline of FV- and IC-HCV RNA was similar between the two treatment groups. At the second phase (day 2-28), the decline of IC was significantly faster in patients treated with IFN plus ribavirin compared with IFN alone [exponential decay slope = 0.079 +/- 0.036 vs 0.048 +/- 0.027 log10/day, P = 0.0248; half-life = 81.1 +/- 21.4 vs 135.1 +/- 61.4 h, P = 0.0053], although the second phase FV-decline was not significantly different between the two treatment groups. The fast second phase decline of IC was associated with sustained virological response to therapy. These results suggest that ribavirin may modulate the humoral immune response against HCV and trigger a favourable response to IFN. In conclusion, analysis of early IC-HCV dynamics is useful for predicting the response to therapy and for understanding the mechanism of action of antiviral drugs in chronic hepatitis C patients.

Adult↗