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Biomedical subjects

K Kojima

Publications and source records attributed to K Kojima.

At least 253 records · Page 14Linked to original sources

The serum resistance of malaria-infected erythrocytes.

IgG and IgM antibodies were detected on non-parasitized as well as parasitized erythrocytes (E) from mice surviving over 15 days after infection with rodent malaria, Plasmodium berghei, whereas C3 was detected exclusively on parasitized E. Parasitized E, however, were quite resistant to the haemolytic activity of guinea pig complement and effectively inactivated human C3b to iC3b on their surface. Similarly, parasitized E were extremely resistant to homologous complement as assessed by haemolysis and C3 binding even when regulatory proteins (decay-accelerating factor, DAF; complement receptor related gene y, Crry; heat-stable antigen, HSA) were blocked with specific antibodies. DAF and Crry were equally expressed on both normal E and parasitized E from mice within a week post-infection; therefore, molecules that inhibit the haemolysis or C3 binding of parasitized E appear to be independent of DAF and Crry. Unexpectedly, the molecular forms of HSA and DAF in parasitized erythrocyte membranes were found to be different from those of normal erythrocyte membranes: DAF was detected as three bands (85,000, 64,000 and 30,000 MW) by immunoblotting. HSA was detected as more highly glycosylated forms than normal HSA. These alterations of DAF and HSA could be explained by the modification of membrane proteins and polysaccharides induced by parasitization, and we hypothesize that these changes of membranes or membrane proteins are involved in the resistance of parasitized E against homologous complement.

Animals↗

Prognostic value of Ki-67 antigen and p53 protein in urinary bladder cancer: immunohistochemical analysis of radical cystectomy specimens.

OBJECTIVE: To investigate the role of tumour proliferation and p53 expression as a marker of survival in patients with urinary bladder cancer who undergo radical cystectomy. PATIENTS AND METHODS: Samples were obtained from 31 patients (29 men and two women, mean age 66.0 years, range 46-80) with transitional cell carcinoma of the bladder who underwent radical cystectomy. The 31 formalin-fixed radical cystectomy specimens were stained immunohistochemically for Ki-67 antigen and p53 protein using MIB1 and p53 antibodies, respectively, and the results correlated with tumour grade, stages and prognosis. RESULTS: The Ki-67 index was significantly greater in high-grade tumours and in those overexpressing p53 (> 20% positive nuclei). Patients whose tumour samples had a high Ki-67 index (> 32%) had a significantly worse prognosis than those with a lower index (P < 0.01). There was a similar correlation between Ki-67 index and prognosis in high-risk patients (grade 3 and pT3-4; P < 0.05). Although the associations between tumour grade, stage and p53 expression were not statistically significant, patients whose tumour samples overexpressed p53 had a lower survival rate (P < 0.05). No patients with tumours having a low Ki-67 and low p53 index (n = 14) died of urinary bladder cancer during the follow-up. CONCLUSION: These results suggest that immunohistochemical analyses for Ki-67 and p53 are useful prognostic indicators in patients with urinary bladder cancer who undergo radical cystectomy; the prognostic role of these markers was particularly important in high-risk (grade 3 and pT3-4) patients.

Aged↗

The thymus and self-tolerance: co-existence of encephalitogenic S100 beta-specific T cells and their nominal autoantigen in the normal adult rat thymus.

The adoptive transfer of auto-reactive T cells specific for S100 beta protein mediates experimental autoimmune panencephalomyelitis, an inflammatory autoimmune disease of the nervous system and eye. However, unlike classical encephalitogenic autoantigens which are components of the myelin membrane and restricted to the nervous system, S100 beta is expressed by many different cell types in a wide variety of peripheral tissues. We now report that S100 beta is also expressed within the rat thymus from embryonic day 16 through to adulthood at which time point the protein is localized within stroma cells of the thymic medulla. However, despite the continued expression of this autoantigen within the thymic microenvironment it proved possible to isolate encephalitogenic, S100 beta-specific CD4+ alpha beta TCR T cell lines from the naive adult rat thymus. These T cell lines were highly specific for S100 beta, and following activation in vitro and adoptive transfer initiate an inflammatory response in the central nervous system and eye of naive syngeneic recipients. These observations provide additional evidence that clonal deletion of autoaggressive T cell clones in the thymus is leaky. In this case allowing potentially autoaggressive T cell clones specific for S100 beta, a non-myelin autoantigen expressed in the nervous system, thymus and many peripheral tissues, to become an intrinsic component of the normal immune repertoire.

Animals↗

Ultrastructural background of albuminuria in rats with passive Heymann nephritis.

BACKGROUND: Although it is widely known that proteinuria in rats with passive Heymann nephritis (PHN) is prevented by treatment with cobra venom factor (CVF), the precise mechanisms of complement-dependent proteinuria have not been fully elucidated. The aim of this study was to evaluate morphologically whether the size of subepithelial electron-dense deposits (EDDs) contributes to the onset of albuminuria. METHODS: The size of subepithelial EDDs and anionic sites in the lamina rarae externa (LRE) overlaid with subepithelial EDDs were evaluated by ruthenium red and compared between PHN and PHN treated with CVF in rats. RESULTS: Overt albuminuria was present on days 3 and 4 after injection of anti-Fx1A. CVF-treatment of rats with PHN prevented albuminuria (PHN + CVF: n = 6) (53.6 +/- 38.8 vs 1.02 +/- 0.55 mg/day, P < 0.01, on day 4). Rat C3 was detected along the glomerular capillary walls on day 4 post-injection in rats with PHN, but not in rats with PHN + CVF. Subepithelial EDDs were observed in both groups. Quantitative morphometric analysis revealed that CVF-treatment decreased the size of subepithelial EDDs as well as the extent of retraction of glomerular epithelial cells. In both groups the density of anionic sites in the LRE overlaid with EDDs was decreased compared with the LRE without subepithelial EDDs. However, no difference was noted between the two groups. CONCLUSIONS: Depletion of serum complement decreases subepithelial EDDs as well as the number of sites with decreased anionic charge underlying the EDDs. Thus, the size of subepithelial EDDs plays a pivotal role in the onset of albuminuria.

Albuminuria↗

Selective removal of plasma components by high-performance immunoaffinity chromatography.

Affinity chromatography employing immobilized antibody is a rapid and specific technique for isolating biologically active materials from different sources, and high-performance immunoaffinity chromatography (HPIAC) has been used to isolate antibodies and antigens for medical application. In an attempt to resolve the problem of amyloid deposition in dialysis patients, we used HPIAC to specifically remove beta2-microglobulin from human plasma. The use of a membrane as an affinity ligand support was also studied. The specific antibody immobilized on a membrane was highly effective for removal of rat immunoglobulin E passed through an extracorporeal circulation system (ECS). Then we investigated the removal of injected human serum amyloid P component from the blood of rats by means of the ECS. Biocompatibility of the specific antibody-bearing immunoaffinity membrane was also examined in terms of nonspecific binding of other plasma components. These techniques should prove useful for medical application and may have broad applicability for the elimination of any unwanted plasma component.

Animals↗

Characterization of human p33/41 (annexin IV), a Ca2+ dependent carbohydrate-binding protein with monoclonal anti-annexin IV antibodies, AS11 and AS17.

p33/41 (annexin IV) is a member of the family of Ca(2+)-dependent phospholipid binding proteins known as annexins. We previously described that bovine kidney p33/41 (annexin IV) has Ca(2+)-dependent carbohydrate binding activity. In this study, we purified human p33/41 (annexin IV) from the HT29, human colon adenocarcinoma cell line, as well as the bovine kidney annexin by affinity chromatography. Then, we prepared recombinant human p33/41 (annexin IV) expressed in Escherichia coli. The apparent size and the Ca(2+)-dependent carbohydrate binding properties of purified recombinant p33/41 (annexin IV) were indistinguishable from those of the bovine kidney protein. We also performed inhibition assays of carbohydrate binding and of phosphatidylserine/phosphatidylcholine liposome binding of recombinant p33/41 (annexin IV) with anti-p33/41 monoclonal antibodies (AS11 and AS17). We determined the epitopes recognized by the monoclonal antibodies by Western blot analysis using deleted-recombinant p33/41 (annexin IV). The monoclonal antibodies recognized domain 1 and/or 2 of p33/41 (annexin IV). The results of the inhibition assays and the determination of the epitope showed that a carbohydrate binding site is located at domains 3 and 4 of p33/41 (annexin IV) and on the cell surface.

Annexin A4↗

Effect of karasurin-A on nitric oxide production by murine macrophages and mitogenic response of murine splenocytes in vitro.

We studied the effect of karasurin-A, a type-I ribosome-inactivating protein (RIP) isolated from fresh root tubers of Trichosanches kirilowii MAX. var. japonica KITAMURA, on the mitogenic response of murine splenocytes and nitric oxide (NO) production by murine peritoneal macrophages in vitro. Karasurin-A inhibited the lymphocyte proliferation by LPS, ConA and PHA and NO production by LPS at non-cytotoxic concentrations (10-1000 ng/ml for splenocytes and 10-100 ng/ml for macrophages, respectively). These data suggest that karasurin-A has immunosuppressive activity in vitro.

Animals↗

Minor saponins from Tetrapanax papyriferum.

Four new minor saponins, papyrioside LE-LH, were isolated from the leaves of Tetrapanax papyriferum, and their structures were determined on the basis of spectroscopic evidence.

Chromatography, High Pressure Liquid↗

Endoscopic sphincterotomy assisted by percutaneous transhepatic choledochal tube: a preliminary report.

We report a method of endoscopic retrograde sphincterotomy in patients in whom the optimal viewing of the papilla of Vater is hardly obtained. Percutaneous transhepatic cholangiodrainage (PTCD)-tube is placed under ultrasonographic guidance. PTCD-tube coming out of the papilla of Vater is observed by the endoscope and the guide wire inside the shpincterotome is inserted into the PTCD-tube. Sphincterotome is advanced into the common bile duct by the guidance of the guide wire and PTCD-tube. Sphincterotomy is performed in a usual fashion. Two patients with previous history of gastrectomy underwent this procedure with successful results. This method should be tried when usual method of EST is difficult and unsuccessful.

Aged↗

Multiple gastric carcinoids and pituitary adenoma in type A gastritis.

A 48-year-old male with type A atrophic gastritis developed multiple gastric carcinoids and a pituitary adenoma. Laboratory tests revealed high levels of serum gastrin and growth hormone (GH). He underwent subtotal gastrectomy, resulting in a return of the previously elevated gastrin level to normal. Serum GH concentration remained high. Three months after the surgery, the pituitary tumor, composed greatly of GH-immunoreactive cells, was partially removed. Since hypergastrinemia plays a pivotal role in gastric carcinoid formation and induces GH-releasing factor (GHRH) release resulting in GH-producing pituitary tumor formation, GH-producing pituitary adenoma might be a clinical manifestation in type A gastritis.

Adenoma↗

Menaquinone-4 accumulation in various tissues after an oral administration of phylloquinone in Wistar rats.

The distributions of phylloquinone (PK) and menaquinone-4 (MK-4) in various tissues were assessed after the oral administration of phylloquinone. Wistar rats were fed a vitamin-K-deficient diet for nine days, fasted for 24 h and then given phylloquinone orally at 4 mg/kg body weight. Rats were sacrificed 0, 6, 12 and 24 h after the administration, and an analysis was made of the vitamin K analogues in the plasma, liver, brain, testis, kidney and spleen. The phylloquinone concentration in plasma and the tissues reached a peak 6 h after the oral administration of phylloquinone. By contrast, the concentration of MK-4 peaked in the liver, plasma, kidney and spleen at 12 h, and in brain and testis at 24 h. This data suggests that the ingested phylloquinone was probably converted into MK-4 within the tissues themselves, rather than via hepatic metabolism. The evidence for this is that, after phylloquinone administration, (i) in each of the tissues, the MK-4 concentration increased much more slowly than that of phylloquinone, and (ii) the MK-4 concentration in the plasma and liver reached only much lower levels than those seen in other tissues.

Administration, Oral↗

[The role of serum soluble interleukin 2 receptor (sIL-2R) levels in patients with renal cell carcinoma].

PURPOSE: The correlation between the serum soluble interleukin-2 receptor (SIL-2R) levels and clinical stage is demonstrable in a variety of non-Hodgkin lymphomas. The prognostic significance of sIL-2R levels in the serum of patients with renal cell carcinoma (RCC) was investigated. METHOD: sIL-2R were measured in patients with RCC (n=39) and normal control (n=6) by the enzyme immunoassay technique. Cases of RCC were classified according to the clinical stage, pathological grade and growth type. The IL-2R expression of RCC was evaluated by RT-PCR. RESULT: The serum sIL-2R levels of patients with RCC showed significantly higher values than those of controls (p < 0.05). The serum sIL-2R levels in RCC were closely associated with the stage, grade and growth type of disease. The patients with high serum sIL-2R level (> = 1,000 U/L) exhibited a significantly poorer prognosis than those with low serum sIL-2R level (<1,000 U/L). The band of IL-R was detected only by using the template from the mRNA extracted from a resected tumor tissue of the RCC but not from the RCC cell lines. CONCLUSION: It was suggested that the measurement of serum sIL-2R levels is useful for predicting the prognosis.

Adult↗

Arterial vascular abnormality accompanying cerebral cortical dysplasia.

We report a case of dysplastic arterial vascular abnormality in a 32-year-old man with overlying neuronal cell migration disorder. MR images showed a thickened left insular cortex adjacent to the abnormal vascular network. These findings suggest the possibility of leptomeningeal damage during neuronal cell migration as the cause of the overlying vasculopathy. The true pathogenesis of these seemingly associated abnormalities is unknown.

Adult↗

Intraarterial infusion of papaverine in experimental cerebral vasospasm.

PURPOSE: To determine the effectiveness of intraarterial infusion of papaverine hydrochloride (PPV) in an experimental model of cerebral vasospasm and to measure the mean blood flow velocity of the middle cerebral artery (MCA). METHODS: Seven Japanese monkeys were divided into three groups: those studied 3 days-after surgery (the third-day group, n = 3); those studied 7 days after surgery (the seventh-day group, n = 3); and a control group (n = 1). Vasospasm was induced in the experimental groups by placing a blood clot in the subarachnoid space around the top of the internal carotid siphon. PPV (5 mg/kg) was infused (over 60 minutes) into the internal carotid artery (ICA). The vascular diameters of the ICA and MCA were measured on angiograms before and after infusion. The mean blood flow velocity in the MCA was measured on transcranial Doppler sonograms before and 24 hours after infusion. After fixation, the MCA was dissected out, stained, and examined microscopically. RESULTS: After vasospasm induction, both arteries were narrowed more than 30% in the third-day group and more than 50% in the seventh-day group. After PPV infusion in both groups, vascular dilatation of about 20% was seen. The mean increase in blood flow velocity in the third-day group (30%) was smaller than in the seventh-day group (70%). The mean blood flow velocity in the MCA decreased by about 30% in both groups, but increased again after 24 hours nearly to the level before PPV infusion. The intimal layer was more corrugated in the seventh-day group, and hypertrophy in the smooth muscle layer was also seen. Clinical examination showed no neurologic deficit in the third-day group 24 hours after PPV infusion; neurologic deficits were observed in the seventh-day group. CONCLUSION: PPV infusion may be more effective in early stages of vasospasm when vascular walls have fewer histologic changes.

Animals↗

Experimental autoimmune encephalomyelitis: the antigen specificity of T lymphocytes determines the topography of lesions in the central and peripheral nervous system.

Recent studies on autoimmune encephalomyelitis and neuritis reveal that many different antigens of the central (CNS) and peripheral nervous system may become targets of an encephalitogenic T-cell response. The aim of this study was to determine the influence of T-cell specificity on the pathology of autoimmune-mediated inflammation in the nervous system. Autoimmune encephalomyelitis was induced by the adoptive transfer of CD4+ T-line cells specific for either myelin basic protein, myelin oligodendrocyte glycoprotein (MOG), myelin-associated glycoprotein, S100 beta, or glial fibrillary acidic protein. The severity of the inflammatory response was antigen- and dose-dependent. With the exception of MOG-specific T-line cells, all autoreactive T-cell lines induced inflammation in the CNS and peripheral nervous system. In the myelin-basic-protein-mediated model, the spinal cord was most severely affected with only minor inflammation in the forebrain. In contrast, both MOG- and myelin-associated-glycoprotein-specific T cells induced a far higher density of lesions in the periventricular and cerebellar white matter. S100 beta- and glial-fibrillary-acidic-protein-specific T cells mediated particularly severe inflammation in the gray matter. In addition to these topographic differences, antigen specificity also influenced the extent of both parenchymal inflammation and macrophage activation in the CNS. However, irrespective of the specificity or number of T cells transferred, the major neuropathologic correlate with disease severity was the absolute number of activated macrophages recruited into the CNS parenchyma (r = 0.9; p < 0.0001). This study suggests that differences in lesion distribution in multiple sclerosis patients may reflect differences in the antigen specificity of an encephalitogenic T-cell response.

Amino Acid Sequence↗