Alterations in the chondroitin sulfate chain in human osteoarthritic cartilage of the knee.

OBJECTIVE: To determine whether the structure of chondroitin sulfate (CS) in cartilage is reflected by the degree of cartilage degeneration in patients with osteoarthritis (OA) of the knee and to determine how CS biosynthesis affects cartilage degeneration. DESIGN: Two osteoarthritic cartilage samples were obtained from medial femoral condyle (MFC) and lateral femoral condyle (LFC) of 24 knees with end-stage OA. The samples were assigned to two groups as follows: lesion and remote cartilage were adjacent to and remote from the osteoarthritic cartilage, respectively. Histological grade was determined according to the Mankin score. The CS concentration and chain length were determined using high-performance liquid chromatography (HPLC) and gel filtration chromatography, respectively. Expression of the gene encoding CS glycosyltransferase was evaluated using a real-time quantitative polymerase chain reaction (qPCR) assay. These results were compared between lesion and remote cartilage. RESULTS: The Mankin score indicated that lesion cartilage was more degraded compared with remote cartilage. Although the CS levels varied among individuals, the mean CS concentration and chain length were significantly lower and shorter in lesion cartilage than in remote cartilage, respectively (concentration: 12.04 vs 14.84 µg/mg wet weight, P = 0.021; chain length: 5.36 vs 6.19 kDa, P = 0.026). Three genes encoding CS glycosyltransferases (CHPF, CSGALNACT1, CSGALNACT2) were expressed at lower levels in lesion cartilage. CONCLUSIONS: In the osteoarthritic knee, the CS concentration and chain length were reduced closer to the more degraded cartilage with decreasing CS glycosyltransferase gene expression. Inhibition of CS glycosyltransferase gene expression may reduce CS chain length, which may contribute to OA progression.

Enhanced removal of chemical oxygen demand, nitrogen and phosphorus using the ameliorative anoxic/anaerobic/oxic process and micro-electrolysis.

Synthetic wastewater was treated using a novel system integrating the reversed anoxic/anaerobic/oxic (RAAO) process, a micro-electrolysis (ME) bed and complex biological media. The system showed superior chemical oxygen demand (COD), total nitrogen (TN) and total phosphorus (TP) removal rates. Performance of the system was optimised by considering the influences of three major controlling factors, namely, hydraulic retention time (HRT), organic loading rate (OLR) and mixed liquor recirculation (MLR). TP removal efficiencies were 69, 87, 87 and 83% under the HRTs of 4, 8, 12 and 16 h. In contrast, HRT had negligible effects on the COD and TN removal efficiencies. COD, TN and TP removal efficiencies from synthetic wastewater were 95, 63 and 87%, respectively, at an OLR of 1.9 g/(L·d). The concentrations of COD, TN and TP in the effluent were less than 50, 15 and 1 mg/L, respectively, at the controlled MLR range of 75-100%. In this system, organics, TN and TP were primarily removed from anoxic tank regardless of the operational conditions.

Quantification of hepatitis C virus in patients treated with peginterferon-alfa 2a plus ribavirin treatment by COBAS TaqMan HCV test.

Extremely low levels of serum hepatitis C virus (HCV) RNA can be detected by COBAS TaqMan HCV test. To investigate whether the COBAS TaqMan HCV test is useful for measuring rapid virological response (RVR) and early virological response (EVR) to predict sustained virological response (SVR), we compared the virological response to PEG-IFN-alfa 2a plus RBV in 76 patients infected with HCV genotype 1 when undetectable HCV RNA by the COBAS TaqMan HCV test was used, with those when below 1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test was used, which corresponded to the use of traditional methods. Among the 76 patients, 28 (36.8%) had SVR, 13 (17.1%) relapsed, 19 (25.0%) did not respond, and 16 (21.0%) discontinued the treatment due to side effects. The positive predictive values for SVR based on undetectable HCV RNA by COBAS TaqMan HCV test at 24 weeks after the end of treatment [10/10 (100%) at week 4, 21/23 (91.3%) at week 8 and 26/33 (78.7%) at week 12] were superior to those based on <1.7 log IU/mL HCV RNA [17/19 (89.4%) at week 4, 27/38 (71.0%) at week 8, and 27/43 (62.7%) at week 12]. The negative predictive values for SVR based on <1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test [46/57 (80.7%) at week 4, 37/38 (97.3%) at week 8, and 32/33 (96.9%) at week 12] were superior to those based on undetectable HCV RNA [48/66 (72.7%) at week 4, 46/53 (86.7%) at week 8, and 41/43 (95.3%) at week 12]. The utilization of both undetectable RNA and <1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test is useful and could predict SVR and non-SVR patients with greater accuracy.

Magnetic properties of hydrothermally recrystallized magnetite crystals.

The discrepancy between the magnetic hysteresis properties of magnetite crystals that are precipitated from solution (<0.3 micrometer) and of crushed sifted grains (>0.3 micrometer) is not an inherent property of magnetite but is caused by the highly stressed state of crushed material and by adhering finer fragments. The size trends of magnetic properties exhibited by submicrometer-size precipitated grains continue in the size range from 1 micrometer to 1 millimeter in a set of hydrothermally recrystallized magnetite crystals. Coercive forces of these narrowly sized crystals follow a power law over a wide size range (0.1 micrometer to 1 millimeter) as predicted by theory. Dislocation etch pits show similar dislocation densities for hydrothermally grown (3 x 10(10) meter (-2)) and natural (1 x 10(10) meter(-2)) magnetite crystals. Hysteresis parameters of hydrothermally grown crystals are similar to those of natural crystals but are about one-fifth of those for crushed grains.

Effects of variations of extracellular polymeric substances and soluble microbial products on activated sludge properties during anaerobic storage.

Anaerobic storage always takes place in wastewater treatment plants or sludge handling processes. Although extracellular polymeric substances (EPS) and soluble microbial products (SMP) are well known to be the two important chemical parameters to influence sludge properties, few studies have demonstrated the coexisting effects of the two biopolymers on sludge characteristics during anaerobic storage of activated sludge. The experiments, conducted with acetate as the substrate at 35 degrees C and 25 degrees C and with glucose at 35 degrees C, indicated that EPS content decreased significantly in the first two or three days and later slightly increased in all runs, while SMP concentration varied gradually from 66-105mg l(-1) to 330-420mg 1(-1), increasing almost linearly with anaerobic storage time. All the components in EPS decreased after anaerobic storage, especially protein, which was the dominant organic compound in both EPS and SMP with more than 60% of the total amounts of the two biopolymers. Protein and DNA in SMP increased to a large extent and mainly contributed to the three-to five- fold increase in the total amount of SMP, while carbohydrates in SMP remained at a relatively low level. From statistical analysis, some major correlations could be obtained: a weak correlation existed between SMP and EPS; SMP were much more significantly correlated than EPS with sludge properties (biomass, specific resistance to filtration, sludge volume index and relative hydrophobicity of sludge surface). The results indicated that SMP, not EPS, significantly influence the sludge dewatering and settling properties, being deteriorated by more SMP production from cell lysis during anaerobic storage.

Effects of nutrient addition on phenol biodegradation rate in biofilm reactors for hypersaline wastewater treatment.

Hypersaline wastewater, generated by many industrial activities, is difficult to treat through conventional biological processes. In this kind of hypersaline environment, complex nutrients are needed for the normal growth of many microorganisms. For this paper, the organisms were taken from a municipal wastewater treatment plant and acclimated to 15% salinity in a biofilm treatment process (Sequencing Batch Biofilm Reactor) during the treatment of phenol-containing synthetic wastewater. They are used to evaluate the effects of nutrient addition on the phenol biodegradation rate. Adding yeast extract, glucose, KCl and four mineral nutrients into the shaking flasks containing wastewater and cultivating organisms, revealed phosphate as the crucial nutrient stimulating phenol biodegradation at 15% salinity. The operation results of the sequencing batch biofilm reactor indicates that phosphate content increased up to five times the original level can increase the phenol removal rate by 150%. A 99% phenol removal efficiency could be achieved by shortening the reaction time in the biofilm reactor from 40 h to 16 h, compared with basic nutrients added. In this article we applied an applicable and effective shaking-culture method to determine nutrient requirements in biotreatment processes without stopping the running reactors.

Discovery of a non-peptide small molecule that selectively mimics the biological actions of calcitonin.

Calcitonin (CT), a 32-amino acid peptide hormone secreted mainly from the thyroid gland, plays an important role in maintaining bone homeostasis. To discover non-peptide small molecules with biological actions similar to those of CT, a cell-based screening of an in-house chemical library was performed and a pyridone derivative (SUN B8155) was identified. Like CT, it elevated cyclic AMP (cAMP) levels in T47D and UMR106-06 cells which endogenously express human and rat CT receptor, respectively. SUN B8155 also stimulated cAMP formation in cells expressing recombinant human CT receptor, but not in those expressing human parathyroid hormone/parathyroid hormone-related peptide receptor. Accumulation of cAMP in T47D cells was blocked by a selective antagonist of CT receptor, salmon CT(8-32), whereas SUN B8155 did not displace the specific binding of [(125)I]CT to the receptor. Our results suggested that the compound selectively interacts with the CT receptor by a mechanism similar to but probably different from that of CT itself. In rats, intraperitoneal administration of SUN B8155 significantly lowered serum calcium levels, like CT. Our results demonstrate, for the first time, that the biological activities of the newly identified small molecule can mimic that of CT, acting via the CT receptor.

Inhibition of experimental metastasis and cell adhesion of murine melanoma cells by chondroitin sulfate-derivatized lipid, a neoproteoglycan with anti-cell adhesion activity.

Chondroitin sulfate dipalmitoylphosphatidylethanolamine (CS-PE), when immobilized onto substratum, inhibited the adhesion of B16F10 mouse melanoma cells to fibronectin-coated dishes (anti-adhesion activity). CS-PE showed the most potent anti-adhesion activity for the melanoma cells among various GAG-PEs. CS-PE also inhibited the adhesion of B16F10 cells to Matrigel and the invasion of the cells into Matrigel. In the in vivo system of experimental metastasis, administration of B16F10 cells with CS-PE into C57BL/6 mice significantly inhibited lung metastasis. The inhibition degree of CS or hyaluronic acid-PE was lower than CS-PE. CS-PE administered intravenously into mice before the injection of B16F10 cells also inhibited metastasis. Pretreatment of B16F10 cells with CS-PE caused some but a lower degree of inhibition. When CS-PE was injected intravenously into mice, more binding in the lung was found than when CS was injected. CS-PE but not CS inhibited the retention in the lung of fluorochrome-labeled B16F10 cells when injected intravenously into mice. Since there was no significant effect of CS-PE on the viability and growth of B16F10 cells, the results suggest that CS-PE immobilized onto the subendothelial matrix may prevent melanoma cells from adhering to the subendothelial substrata of lung capillaries and inhibit subsequent invasion processes of metastasis.

A novel immunization procedure for production of anti-cholecystokinin-specific antiserum of low cross-reactivity.

An anti-cholecystokinin octapeptide (CCK-8) antibody without cross-reactivity with pentagastrin, whose amino acid sequence is identical with the carboxy-terminal portion of CCK-8, was produced by immunization with CCK-8-keyhole limpet hemocyanin and injection of a conjugate of pentagastrin and a copolymer of D-glutamic acid and D-lysine to inhibit production of antibody cross-reacting with pentagastrin.

Leukocyte function-associated antigen 1-dependent adhesion of rat hepatoma AH66F cells and inhibition by protein kinase C inhibitors.

When rat ascites hepatoma AH66F cells were incubated on a mesothelial cell (M-cell) layer for 1 hr, the adhesion rate of the cells to M-cells was ca. 46%. The protein kinase C (PKC) inhibitors, N-(2-methylpiperazyl)-5-isoquinolinesulfonamide (H-7) and N-ethoxycarbonyl-7-oxostaurosporine (NA-382), inhibited the adhesion of AH66F cells in a concentration-dependent manner, and the effect of NA-382 appeared after a treatment of more than 24 hr. The decreased adhesion rate after treatment with NA-382 for 48 hr was not further inhibited by addition of monoclonal antibodies of leukocyte function-associated antigen-1 (LFA-1) alpha- and beta-chains and intercellular adhesion molecule-1 (ICAM-1) (WT.1, WT.3, and 1A29, respectively). The expression of LFA- 1 alpha- and beta-chains on the surface of the plasma membrane of AH66F cells was decreased after treatment with NA-382 for 48 hr; treatment with a potent inhibitor of cyclic AMP-dependent protein kinase, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), did not affect the cell adhesion and the expression of LFA-1 molecules on AH66F cells. These results suggest that the expression of LFA-1 molecules on AH66F cells is regulated through the PKC pathway.

Oxitropium bromide improves exercise performance in patients with COPD.

Inhaled anticholinergics may be the first-line therapy for stable COPD. However, the effect of inhaled anticholinergic agents on exercise capacity is still controversial. Fourteen patients with stable COPD (age, 64.6 +/- 5.9 years) completed a randomized, double-blind placebo-controlled crossover trial. All the patients were studied by symptom-limited progressive cycle ergometry before and 90 min after the inhalation of either oxitropium bromide, 800 micrograms, or an identical placebo. Spirometry was assessed before and after each exercise test. While FEV1 averaged 0.85 +/- 0.34 L at 90 min after the inhalation of placebo, FEV1 was 1.01 +/- 0.41 L at 90 min after the inhalation of oxitropium, 800 micrograms (significant from placebo, p < 0.001). The maximal workload of 94.0 +/- 25.8 W after oxitropium administration was significantly greater than the 87.6 +/- 24.7 W measured after placebo (p < 0.01). The maximal minute ventilation was 40.2 +/- 12.3 L/min after oxitropium inhalation and 36.8 +/- 10.5 after placebo inhalation (p < 0.05). The differences in maximal oxygen consumption, maximal carbon dioxide production, and maximal heart rate between oxitropium and placebo inhalation also were statistically significant (p < 0.05, p < 0.05, and p < 0.01, respectively). There was a significant correlation between the change in maximal workload and the change in FEV1 before and after inhalation (r = 0.625, p < 0.01). The inhalation of oxitropium bromide, 800 micrograms, can improve the exercise capacity of patients with stable COPD. It is suggested that the effect is due to the bronchodilation induced by this drug.

The additive effect of theophylline on a high-dose combination of inhaled salbutamol and ipratropium bromide in stable COPD.

STUDY OBJECTIVE: To determine the additive effect of oral theophylline in patients with stable COPD who received both inhaled salbutamol, 400 micrograms, and ipratropium bromide, 80 micrograms, four times daily administered with a metered-dose inhaler. DESIGN: Twenty-four male patients with stable COPD (FEV1, 0.96 +/- 0.43 L; 36.8 +/- 17.0 percent predicted [% pred]) completed a randomized, double-blind, placebo-controlled crossover trial with oral theophylline for 4 weeks. MEASUREMENTS AND RESULTS: The average serum theophylline level was 15.0 +/- 5.5 micrograms/mL during treatment. On the whole, without inhalation of bronchodilators, FEV1 was 0.93 +/- 0.42 L during the placebo period and 1.00 +/- 0.43 L (significantly different from placebo; p < 0.01) during the theophylline period. At 15 and 60 min after inhalation of salbutamol, 400 micrograms, and ipratropium, 80 micrograms, the FEV1 with placebo was 1.12 +/- 0.43 L and 1.14 +/- 0.46 L, respectively, and the FEV1 with theophylline was 1.18 +/- 0.45 L (p < 0.01) and 1.20 +/- 0.47 L (p < 0.01), respectively. Daily peak expiratory flow rate also improved. Daily symptom scores were not significantly different between theophylline and placebo periods. Nevertheless, eight patients reported a subjective benefit during the theophylline administration period, and they were thus considered subjective responders. While FEV1 after inhalation was significantly improved during the theophylline periods in subjective responders (change in FEV1 between theophylline and placebo treatment 15 min after inhalation, 3.1 %pred; 60 min, 3.5 %pred), postbronchodilator FEV1 was not significantly different between the placebo and theophylline periods in subjective nonresponders (15 min, 1.7 %pred; 60 min, 1.6 %pred). CONCLUSIONS: On the whole, theophylline has a small bronchodilating effect but does not improve the symptoms of patients with stable COPD. However, one third of patients with COPD may respond subjectively to theophylline. The additive bronchodilating effect of theophylline may be related to the symptomatic improvement in subjective responders.

Combined effects of radiation and caffeine on embryonic development in mice.

The combined effect of radiation and caffeine has been studied in mouse embryos. Radiation and/or caffeine were administered to ICR mice on Day 11 of gestation. Intrauterine death, gross malformation, and fetal body weight were selected as indicators of effects. Doses of whole-body gamma irradiation were 0.5 to 2.5 Gy and those of caffeine were 100 and 250 mg/kg maternal body wt. Intrauterine mortality increased with increasing radiation dose; this trend was more remarkable in combination with caffeine. Gross malformations such as cleft palate and defects of forelegs and hindlegs appeared frequently in the fetuses treated with both radiation and caffeine. Decreased fetal weight was observed even in mice treated with 0.5 Gy of radiation or 100 mg/kg caffeine. There was a linear relationship between dose and reduction of fetal weight. The fetal weight was a sensitive, precise, and easy-to-handle indicator for the effects of growth retardation. Intrauterine mortality and frequencies of cleft palate and defects of forelegs and hindlegs were higher than the sum of those induced by radiation and by caffeine separately. The results indicated that the combined action of radiation and caffeine on intrauterine death and malformations was synergistic.

Study of repeated arterial infusion chemotherapy with a subcutaneously implanted reservoir for advanced hepatocellular carcinoma.

We performed repeated arterial infusion chemotherapy (RAIC) in 114 advanced hepatocellular carcinoma (HCC) patients, using a subcutaneous reservoir implanted under ultrasonic guidance. In 60 patients, this was the initial therapy for the primary tumor and the other 54 patients being treated for recurrent tumor. One hundred and seventy-one patients with advanced HCC who had been treated by transcatheter arterial embolization (TAE) or single bolus arterial infusion chemotherapy before RAIC was available served as historical controls. In 97 patients, anticancer agents (4'-epidoxorubicin or acurarubicin) and Lipiodol emulsion were used, and in 17, anticancer agents alone were given. The response rates were 39.2% in the Lipiodol group and 17.6% in the non-Lipiodol group. The dose of Lipiodol and the degree of liver invasion were the most important factors influencing the response rate. The 1-, 2-, and 3-year survival rates were 55.0%, 30.9%, and 21.2%, respectively. The long-termsurvival was compared in relation to Child's classification and the presence or absence of portal vein tumor thrombosis (PVTT). In non-PVTT patients, the results of initial therapy and therapy for recurrence were similar, but recurrent Child's C patients showed a poorer prognosis. In PVTT patients, initial therapy had a better prognosis than treatment for recurrence, but initial Child's C patients had a poor long-termprognosis. During the observation period, no severe complications were encountered, but in Child's C patients, hepatic function sometimes deteriorated. Compared with the results in the 171 controls, RAIC was more useful for advanced HCC as initial therapy, and it was also beneficial for the treatment of recurrence after TAE.

Highly malignant rat hepatoma AH66F cells respond to ascitic fluid.

Rat ascites hepatoma (AH) 66F cells are more maligant than AH130 cells. AH66F cells grew faster than AH130 cells in media supplemented with both 5% fetal calf serum (FCS) and 5% ascites fluid (ASF), which is obtained from rats bearing these cells. The growth of AH66F cells was more accelerated in ASF than in FCS. The motility of AH66F cells was significantly increased by ASF, while the cells hardly moved in FCS. The growth and motility of AH130 cells were not different in FCS and ASF. Moreover, the adhesion ability of AH66F cells to mesothelial cells (M-cells) isolated from the mesentery was significantly higher than that of AH130 cells just after harvesting from the rats. The fresh AH66F cells adhered to M-cells at about 60%, and the adhesion rate of the cells decreased to about 47% after culturing with 5% FCS for 48 hours but was maintained in the presence of ASF. The adhesion ability of AH130 cells was not changed after incubation with both FCS and ASF. On the other hand, it has been reported that AH66F cells are unique in having leukocyte function-associated antigen-1 (LFA-1) on the outer cell membrane, adhering through interaction with intercellular adhesion molecule-1 (ICAM-1) on M-cells, although AH130 cells are not so efficient as other hepatoma cells. Consequently, the adhesion of AH66F cells to M-cells was inhibited by anti-LFA-1 beta-chain monoclonal antibody and anti-ICAM-1 antibody. When cells were cultured separately with FCS or ASF, and the adhesion molecules were analysed using flow cytometry, the expression of LFA-1 molecules on AH66F cells was not changed by eitherv FCS or ASF, but the ICAM-1 molecule on M-cells was increased time-dependently by ASF. From these results, the high malignancy of AH66F cells attributes to responsibility to ASF for tumor growth and motility and to irregular expression of LFA-1 on the membrane, in comparison to AH130 cells.

Comparison between Japan and North America in the post-hospital course after recovery from an acute coronary event.

We compared the post-hospital prognosis after an acute coronary event (acute myocardial infarction and unstable angina) in 106 patients in Japan vs. 789 patients in North America who were prospectively enrolled in the Multicenter Study of Myocardial Ischemia and were followed-up for an average of 26 months per patients. Risk factors more frequent in Japan were older age, males and smoking at enrollment, but the rest of many risk factors were similar. After adjusting for differences in clinical and medication variables, Cox analyses indicated patients in North America had a significantly greater risk of experiencing a primary end-point (cardiac death, non-fatal myocardial infarction or unstable angina) than patients in Japan (hazard ratio [North America:Japan] = 3.1, P = 0.003). There was a non-significant trend in the restricted end-points (cardiac death or non-fatal myocardial infarction) with North America having more frequent events than Japan (hazard ratio = 2.2, P = 0.12). The long-term outcome after recovery from an acute coronary event is more favorable in Japan than in North America, mostly due to a reduction in subsequent hospitalization for unstable angina. The reason for these findings cannot be explained by differences in the measured risk factors or medications.

Clinical evaluation of sonoelasticity measurement in liver using ultrasonic imaging of internal forced low-frequency vibration.

The aim of this study is to evaluate liver elasticity noninvasively. We have already proposed an ultrasonic imaging system that can reconstruct vibration maps inside tissue under forced mechanical vibration. With this system, shear elastic properties of soft tissue can be evaluated as vibration velocities. Theoretically, these velocities increase with the increase of tissue elasticity. Sonoelasticity imaging was performed on 236 patients with chronic hepatitis and liver cirrhosis, and 50 healthy volunteers. The average of the velocities was 598.8 +/- 151.7 cm/s in healthy volunteers, 984.4 +/- 362.5 cm/s in chronic hepatitis and 1189.0 +/- 411.7 cm/s in liver cirrhosis. The average velocity of Child C group was statistically faster than those of Child A and B groups. Fibrotic rate from biopsy specimens statistically had the strongest positive correlation with velocities. With our system, the degree of liver fibrosis and function can be estimated objectively and noninvasively.

An image analyzing system using an artificial neural network for evaluating the parenchymal echo pattern of cirrhotic liver and chronic hepatitis.

To objectively evaluate the parenchymal echo pattern of cirrhotic liver and chronic hepatitis, we applied an image analyzing system (IAS) using a neural network. Autopsy specimens in a water tank (n = 13) were used to examine the relationship between the diameter of the regenerative nodule and the coarse score (CS) calculated by IAS. CS was significantly correlated with the diameter of the regenerative nodule (p < 0.0001, r = 0.966). CS is considered to be useful for evaluating the coarseness of the parenchymal echo pattern.

Hydrogen-isotopic compositions in Allan Hills 84001 and the evolution of the martian atmosphere.

Hydrogen-isotopic compositions of carbonate and maskelynite in Allan Hills (ALH) 84001 were measured by secondary ion mass spectrometry (SIMS). The delta D values of both minerals show considerable deviation. The deviation seems to be caused by addition of varying amounts of terrestrial water in the case of carbonate. In the case of maskelynite, H is heterogeneously distributed and the deviation in delta D values seems to be due to mixing of this indigenous heavy H with isotopically normal H present in the SIMS chamber. The indigenous delta D value in ALH 84001 seems to be approximately 2000%. Carbonate rather than maskelynite seems to be the main carrier of H in ALH 84001. Because ALH 84001 is approximately 4 Ga old, the H-isotopic composition suggests that a large fraction of the initial martian atmosphere had already escaped by 4 Ga.

Use of artificial neural network in the prediction of algal blooms.

A model to quantify the interactions between abiotic factors and algal genera in Lake Kasumigaura, Japan was developed using artificial neural network technology. Results showed that the timing and magnitude of algal blooms of Microcystis, Phormidium and Synedra in Lake Kasumigaura could be successfully predicted. As for the newly occurring dominant Oscillatoria, results were not satisfactory. The evaluation of the importance of factors showed that Microcystis, Phormidium, Oscillatoria and Synedra were alkalophilic. The algal proliferation for Microcystis, Oscillatoria and Synedra decrease due to the increase in total nitrogen, while the growth of Phormidium is enhanced with more nitrogen. In addition, the algal density is affected by zooplankton grazing but with the exception of Phormidium due to it being poor food source. Algal responses to the orthogonal combinations of the external environmental factors, chemical oxygen demand, pH, total nitrogen and total phosphorus at three levels were modeled. Various combinations of environmental factors enhance the proliferation of some algae while other combinations inhibit bloom formation.