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Koji Shirai

Publications and source records attributed to Koji Shirai.

15 recordsLinked to original sources
PubMed2006

A retrospective search for predictors of clinical response to selective granulocyte and monocyte apheresis in patients with ulcerative colitis.

Recently, selective granulocytapheresis (Adacolumn) has appeared as a new treatment for patients with inflammatory bowel disease. This study sought to determine predictors of response to this new nonpharmacologic mode of therapy by retrospectively evaluating 28 patients who received granulocytapheresis after experiencing active ulcerative colitis (UC). Between April 2000 and March 2004, 28 consecutive patients received granulocytapheresis for active UC with the Adacolumn, which is filled with cellulose acetate beads as the column leukocytapheresis carriers; the carriers adsorb granulocytes, monocytes/macrophages, and a small fraction of lymphocytes (FcgammaR and complement receptors bearing leukocytes). Each patient could receive up to 10 Adacolumn sessions, at 2 sessions per week. In 2004, clinical response was retrospectively evaluated. Seven days after the last Adacolumn session, 20 of 28 patients had remission (colitis activity index [CAI] < or =4) including all 8 patients who had their first UC episode. The mean duration of UC in the 8 first episode cases was 3.4 months compared with 40.2 months for all 28 patients and 65.4 months for the 8 nonresponders. The response to Adacolumn was independent of basal CAI. The 8 nonresponders were given conventional medication (CM) or cyclosporine (CsA) if the former failed. Two responded to CM, 3 to CsA, and 3 underwent colectomy. First UC episode and short disease duration appear good predictors of response to granulocytapheresis. Selective granulocytapheresis might be an effective first-line treatment.

Adolescent↗
PubMed2006

Synthesis of silk fibroin-insulin bioconjugates and their characterization and activities in vivo.

The regenerated liquid silk fibroin with an average molecular mass of about 60 kDa consists of 18 kinds of amino acids containing approximately 10% of polar amino acids with hydroxyl and amino groups such as serine and lysine. The liquid silk fibroin is coupled covalently with insulin molecules through these strongly polar side groups by using glutaraldehyde. The physicochemical properties of the silk fibroin-insulin (SF-Ins) bioconjugates were investigated by enzyme-linked immunosorbent assay for the quantitative measurement of insulin. The biological activities of the insulin bioconjugates were characterized in vitro and in vivo. The SF-Ins constructs obtained by 5 h of covalent crosslinking showed much higher recovery (about 70%) and in vitro stability in human serum than bovine serum albumin-insulin (BSA-Ins) derivatives. The results in human serum indicated that the half-life in vitro of the biosynthesized SF-Ins derivatives was 2.1 and 1.7 times more than that of BSA-Ins conjugates and native insulin, respectively. The immunogenicity of the regenerated silk fibroin and the antigenicity of silk fibroin-modified insulin were not observed in both rabbits and rats. The pharmacological activity of the SF-Ins bioconjugates in diabetic rats evidently lengthened and was about 3.5 times as long as that of the native insulin, nearly 21 h. The bioconjugation of insulin with the regenerated silk fibroin greatly improved its physicochemical and biological stability.

Animals↗
PubMed2006

Probucol and atorvastatin decrease urinary 8-hydroxy-2'-deoxyguanosine in patients with diabetes and hypercholesterolemia.

To clarify whether probucol and statins suppress oxidative stress in diabetic patients, we studied the effects of probucol and the statin atorvastatin on urinary 8-hydroxy-2'deoxyguanosine (8-OHdG) levels in diabetics with hypercholesterolemia. A randomized, open study was performed on a total of 36 patients with type 2 diabetes and hypercholesterolemia. The patients were randomly assigned to a probucol group (500 mg/day, n = 18) or an atorvastatin group (10 mg/day, n = 18). During three months, total- and LDL-cholesterol decreased significantly in both groups. LDL-cholesterol was significantly lower in the atorvastatin group than probucol group. HDL-C decreased significantly in the probucol group and did not change in the atorvastatin group. 8-OHdG decreased significantly in both groups after 3 months; 12.4 +/- 7.5 to 8.1 +/- 4.2 ng/mg/Cr in the atorvastatin group (p < 0.05) and 12.3 +/- 8.8 to 6.8 +/- 2.6 ng/mg/Cr in the probucol group (p < 0.05), and these changes did not differ significantly between the two groups. But, in patients with high 8-OHdG levels (more than 10 ng/mg/Cr) before administration, urinary 8-OHdG decreased significantly from 19.5 +/- 4.9 to 9.2 +/- 3.4 ng/mg Cr (p < 0.01) in the atorvastatin group, and from 19.7 +/- 8.2 to 6.67 +/- 2.2 ng/mg Cr (p < 0.01) in the probucol group. Urinary 8-OHdG was significantly lower in the probucol group than in the atorvastatin group after the second and third months of administration (p < 0.05). These results suggest that while probucol and atorvastatin both reduce systemic oxidative stress, probucol might be the more useful in patients with strong oxidative stress.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2006

[A case of interstitial pneumonia accompanying SIADH].

A 75-year-old man was transferred to our hospital on November 28, 2003 because of acute aggravation while being treated for interstitial pneumonia superimposed on pneumoconiosis at a local hospital. Upon admission, oxygen inhalation therapy and antimicrobial chemotherapy were started for the interstitial pneumonia. In addition, since he showed hyponatremia from admission, a saline load was administered and the clinical course was observed. However, disturbance of consciousness developed on January 5, 2004. At that time, the serum sodium was 115mEq/l. Since secretion of antidiuretic hormone (SIADH) had continued despite a low plasma osmolarity, we diagnosed syndrome of inappropriate secretion of antidiuretic hormone (SIADH). We initiated treatment with water restriction and saline load, but no remarkable improvement was observed. From February 7, 40mg /day prednisolone was started because of aggravation of interstitial pneumonia. As a result, the respiratory status and image findings improved, and serum sodium level was normalized. This case was considered to be SIADH secondary to interstitial pneumonia. Among respiratory tract diseases, SIADH is often caused by small cell lung carcinoma, although it may also occur concurrently with other respiratory tract diseases. Since hyponatremia may manifest grave disturbance of consciousness, investigation of the cause is important.

Aged↗
PubMed2005

Total synthesis of (+)-batzelladine A and (-)-batzelladine D, and identification of their target protein.

Asymmetric total synthesis of batzelladine A (1) and batzelladine D (2) has been achieved. Our synthesis of batzelladines features 1) stereoselective construction of the cyclic guanidine system by means of successive 1,3-dipolar cycloaddition reaction and subsequent cyclization, 2) direct esterification of the bicyclic carboxylic acid 35 with the guanidine alcohol 8 or 59 to construct the whole carbon skeleton of batzelladines, and 3) one-step formation of the alpha,beta-unsaturated aldehyde 53 from the primary alcohol 47 with tetra-n-propylammoniumperruthenate (TPAP), providing an efficient route to the left-hand bicyclic guanidine alcohol of batzelladine A (1). With the synthetic compounds 1 and 2 in hand, their target protein was examined by using immobilized CD4 and gp120 affinity gels. The results indicated that batzelladines A (1) and D (2) bind specifically to CD4.

Alkaloids↗
PubMed2005

Contribution of circulating hemocytes to the regeneration of heavy ion beams (12C5+) irradiated hematopoietic organs in the silkworm, Bombyx mori, through the way of phagocytosis of injured cells after invasion.

Heavy ion beam irradiation has promising effects on tumor therapy. Our previous study using the domesticated silkworm, Bombyx mori, showed that this irradiation could seriously damage larval hematopoietic organs but they would regenerate later. In the in vitro irradiation, most hemocytes died when hematopoietic organs and wing discs connected with epidermis were directionally irradiated from epidermis to hematopoietic organ and then cultured so as to exclude circulating hemocytes. A few hemocytes had escaped irradiation according to extremely low hematopoiesis in vitro. Almost no hemocytes could incorporate BrdU at 60 h after irradiation, with which living and proliferating hemocytes are also labeled. In the absence of circulating hemocytes, the irradiation-escaped hemocytes in the organs were not enough for cleaning all dead cells because lots of small dead bodies remained in situ post-irradiation. After irradiating hematopoietic organs in larvae (in vivo irradiation), only a few apoptotic cells were found when given the same length of recovery time, and most hemocytes maintained normal morphology. Many hemocytes incorporated BrdU when tested at the same time as the in vitro irradiation but this number was lower than that measured for control organs. Circulating hemocytes, labeled by fluorescent microbeads through phagocytosis before irradiation, were found to have invaded the in vivo irradiated hematopoietic organs where they help the irradiation-escaped hemocytes to clear dead cells in the process of regeneration. Hematopoiesis of the regenerated hematopoietic organs did not fully recover to the level of the control organs according to the number of hemocytes produced in tissue culture. Some of the released hemocytes obviously underwent apoptosis, suggesting a far-reaching bystander effect of carbon ion beams irradiation on hemocytes inside. From these results, it is suggested that, together with irradiation-escaped hemocytes, the invaded circulating hemocytes took part in the regeneration of heavy ion beams irradiated hematopoietic organs through the way of phagocytosis of injured hemocytes in vivo.

Animals↗
PubMed2005

Synthesis, characterization and immunogenicity of silk fibroin-L-asparaginase bioconjugates.

L-asparaginase (ASNase) is one basic drug in the treatment of acute lymphoblastic leukemia (ALL). Because its half-life time is too short and it is easy to arouse allergic reaction, use in practical clinic is considerably limited. Silk fibroin (SF) with different molecular mass from 40 to 120 kDa is a natural biocompatible protein and could be used as a novel bioconjugate for enzyme modification to overcome its usual shortcomings mentioned above. When the enzyme was bioconjugated covalently with the water-soluble fibroin by glutaraldehyde, the enzyme kinetic properties and immune characteristics in vivo of the resulting silk fibroin-L-asparaginase (SF-ASNase) bioconjugates were investigated in detail. The results show that the modified ASNase was characterized by its higher residual activity (nearly 80%), increased heat and storage stability and resistance to trypsin digestion, and its longer half-life (63 h) than that of intact ASNase (33 h). The abilities of intact and modified ASNases to arouse allergic reaction are 2(4) and 2(1) antibody titers, respectively. Bioconjugation of silk fibroin significantly helps to reduce the immunogenicity and antigenicity of the enzyme. The apparent Michaelis constants of the modified ASNase (K(m(app))=0.844 x 10(-3)mol L(-1)) was approximately six times lower than that of enzyme alone, which suggests that the affinity of the enzyme to substrate l-asparagine elevated when bioconjugated covalently with silk fibroin. SF-ASNase bioconjugates could overcome the common shortcomings of the native form. Therefore, the modified ASNase coupled with silk fibroin has the potential values of being studied and developed as a new bioconjugate drug.

Adjuvants, Immunologic↗
PubMed2005

Probucol delays progression of diabetic nephropathy.

Probucol has antioxidant and cholesterol-lowering effects. This study examined the effect of probucol on progression of diabetic nephropathy. We performed a randomized, open trial on 102 type 2 diabetes patients with clinical albuminuria (urinary albumin excretion >300 mg/g Cr). Fifty-one patients were assigned to probucol treatment (500 mg/day) and 51 to no probucol treatment. Among all patients, 40 who had serum creatinine >or=2mg/dl at baseline were defined as advanced cases. All patients were followed for a maximum 3 years. HbA1c levels were not different between two groups. High-density lipoprotein cholesterol decreased significantly in probucol group. Increase in urinary protein (g/day/month) was significantly greater in non-probucol than in probucol group. Hemodialysis was initiated in 23 patients (10 in probucol group and 13 in non-probucol group). The mean interval to initiation of hemodialysis was significantly longer in probucol group (20.7+/-8.2 months) than in non-probucol group (11.3+/-7.4 months). In advanced cases, increases of both serum creatinine and urinary protein were significantly suppressed in probucol group. In advanced cases, the hemodialysis-free rate was significantly higher in probucol group than in non-probucol group. These results suggest that probucol may suppress the progression of diabetic nephropathy.

Aged↗
PubMed2005

Hemocyte differentiation in the hematopoietic organs of the silkworm, Bombyx mori: prohemocytes have the function of phagocytosis.

Hemocytes isolated from the larval hematopoietic organs of the silkworm were classified following staining with acridine orange and propidium iodide. Among the hemocytes isolated from the hematopoietic organs of whole fifth larval and wandering stages, most were prohemocytes (60%-70%) and oenocytoids (30%-40%). Granulocytes comprised only about 0.5%-1% at the wandering stage and were even rarer at other stages; no spherulocytes or plasmatocytes were found. Therefore, hemocyte differentiation inside larval hematopoietic organs is not as extensive as previously thought. Following 10-30 min in vitro culture of hemocytes isolated from larval hematopoietic organs, many young granulocytes and plasmatocytes appeared. Furthermore, during phagocytosis assays, prohemocytes were seen to adopt the morphology of plasmatocytes, containing fragments of phagocytosed cells. Our results underline the similarities between Drosophila and Bombyx hematopoiesis.

Acridine Orange↗
PubMed2005

Severe hypercholesterolemia associated with decreased hepatic triglyceride lipase activity and pseudohyponatremia in patients after allogeneic stem cell transplantation.

A 55-year-old woman with Ph-negative acute lymphoblastic leukemia in primary induction failure received allogeneic peripheral blood stem cell transplantation from her HLA-compatible sister. Pseudohyponatremia developed due to extreme hypercholesterolemia of 4091 mg/dL accompanied by lipoprotein X and lipoprotein Y. The hypercholesterolemia was caused by cholestasis due to chronic GVHD and ischemic cholangiopathy. In addition, we found that hepatic triglyceride lipase (HTGL) activity was severely decreased, which could be another novel factor causing extreme hypercholesterolemia after allogeneic transplantation. The total cholesterol has been gradually decreasing followed by the improvement of cholestasis with bezafibrate, ursodeoxycholic acid and prednisone treatments, and by a slight increase in HTGL-protein. To our knowledge, this is the first report to describe the association of decreased HTGL with extreme hypercholesterolemia after allogeneic transplantation.

ABO Blood-Group System↗
PubMed2003

Classification of larval circulating hemocytes of the silkworm, Bombyx mori, by acridine orange and propidium iodide staining.

Circulating hemocytes of the silkworm can be classified by fluorescence microscopy following staining with acridine orange and propidium iodide. Based on their fluorescence characteristics, three groups of circulating hemocytes can be distinguished. The first group, granulocytes and spherulocytes, is positive for acridine orange and contain bright green fluorescent granules when observed by fluorescence microscopy. In granulocytes, these green granules are heterogeneous and relatively small. In contrast, in spherulocytes, the green granules appear more homogenous and larger. The second group of hemocytes consists of prohemocytes and plasmatocytes. These cells appear faint green following staining with acridine orange and do not contain any green fluorescent granules in the cytoplasm. Prohemocytes are round, and their nuclei are dark and clear within a background of faint green fluorescence. Inside the nucleus there are one or two small bright green fluorescent bodies. Plasmatocytes are irregularly shaped and their nuclei are invisible. Oenocytoids belong to the third group, and their nuclei are positive for propidium iodide. Therefore, all five types of circulating hemocytes of the silkworm, including many peculiar ones that are difficult to identify by light microscopy, can now be easily classified by fluorescence microscopy following staining with acridine orange and propidium iodide. In addition, we show that hemocytes positive for acridine orange and propidium iodide are in fact living cells based on assays for hemocyte composition, phagocytosis, and mitochondrial enzyme activity.

Acridine Orange↗
PubMed2003

Biliverdin binds covalently to agrobacterium phytochrome Agp1 via its ring A vinyl side chain.

The widely distributed phytochrome photoreceptors carry a bilin chromophore, which is covalently attached to the protein during a lyase reaction. In plant phytochromes, the natural chromophore is coupled by a thioether bond between its ring A ethylidene side chain and a conserved cysteine residue within the so-called GAF domain of the protein. Many bacterial phytochromes carry biliverdin as natural chromophore, which is coupled in a different manner to the protein. In phytochrome Agp1 of Agrobacterium tumefaciens, biliverdin is covalently attached to a cysteine residue close to the N terminus (position 20). By testing different natural and synthetic biliverdin derivatives, it was found that the ring A vinyl side chain is used for chromophore attachment. Only those bilins that have ring A vinyl side chain were covalently attached, whereas bilins with an ethylidene or ethyl side chain were bound in a noncovalent manner. Phycocyanobilin, which belongs to the latter group, was however covalently attached to a mutant in which a cysteine was introduced into the GAF domain of Agp1 (position 249). It is proposed that the regions around positions 20 and 249 are in close contact and contribute both to the chromophore pocket. In competition experiments it was found that phycocyanobilin and biliverdin bind with similar strength to the wild type protein. However, in the V249C mutant, phycocyanobilin bound much more strongly than biliverdin. This finding could explain why during phytochrome evolution in cyanobacteria, the chromophore-binding site swapped from the N terminus into the GAF domain.

Algorithms↗
PubMed2002

Chylomicronemia caused by lipoprotein lipase gene mutation related to a hyper-response of insulin secretion to glucose.

A 39-year-old man with lipoprotein lipase (LPL) deficiency (height 177.7 cm, body weight 67 kg, and body mass index 21.2 kg/m2) showed severe hypertriglyceridemia (2,032 mg/dl). LPL activity and concentration were markedly low in postheparin plasma. LPL gene analysis revealed a homozygous mutation, Asp204 --> Glu in exon 5. Fasting plasma glucose (81 mg/dl) and insulin (2.7 microU/ml) levels were normal. Plasma glucose pattern during oral glucose (75 g) tolerance test was normal, however 30 minutes after glucose-loading the insulin secretion unexpectedly increased to 89.4 microU/ml. These data suggested that chylomicronemia might be related to a hyper-response of insulin secretion to glucose without obesity.

Adult↗