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Biomedical subjects

K Kumano

Publications and source records attributed to K Kumano.

At least 55 records · Page 3Linked to original sources
PubMed1998

Blockade of CD28/B7 interaction suppresses allergic eosinophilic inflammation in mice.

To determine whether the costimulatory signal via CD28/B7 interaction is required for causing allergic inflammation, we examined the effect of administration of CTLA4-Ig, a fusion protein of the extracellular domain of CTLA4 and human IgG1-constant region, at the time of sensitization, on antigen-induced eosinophil infiltration in the trachea of sensitized mice, on IL-2, IFN-gamma, IL-4 and IL-5 production in the airways of the mice and on antigen-specific IgE synthesis in the mice. Administration of CTLA4-Ig at the time of sensitization suppressed antigen-induced eosinophil infiltration into the trachea and antigen-specific IgE production in mice. Furthermore, CTLA4-Ig administration at the time of sensitization suppressed not only IL-2 production but also IFN&hyphengamma and Th2 cytokine IL-4 and IL-5 production in the airways. Because allergic inflammation requires CD4+ T cells producing Th2-type cytokines IL-4 and IL-5, our results suggest that the costimulatory signal via CD28/B7 interaction is important for the generation and activation of Th2 cells and thereby for the development of allergic inflammation.

Abatacept↗
PubMed1998

Saccharides as osmotic agents in peritoneal dialysate: determination of molecular weight essential for more efficient fluid removal.

Glucose has widely been used as an osmotic agent in continuous ambulatory peritoneal dialysis (CAPD) but owing to its low molecular weight (MW), ultrafiltration (UF) in a 6-hour dialysate exchange does not appear sufficient. Thus, in the present study, a search was made to find saccharides that would ensure optimal UF, exceeding that obtained with glucose in a 6-hour dwell period. Rats were intraperitoneally infused with peritoneal dialysate (20 mL/body) containing the same molar concentrations (75.5 mM, 126 mM, or 204 mM) of various osmotic agents including glucose (monosaccharide, MW = 180.16) at concentrations of 1.36%, 2.27%, and 3.86%; maltose (disaccharide, MW = 342.30) at concentrations of 2.58% and 4.32%; maltotriose (trisaccharide, MW = 504.44), at concentrations of 3.81% and 6.36%; and maltopentaose (pentasaccharide, MW = 828.72) at concentrations of 6.26% and 10.4%. Intraperitoneal-fluid volume was measured at 1, 2, 3, 4, and 6 hours. With glucose as the osmotic agent, maximal UF was noted at 2 to 4 hours. UF was more efficient at 6 hours with maltotriose or maltopentaose as the osmotic agent. Even with a trisaccharide or pentasaccharide (molecular weights of 500 to 830), UF at 6 hours was found more efficient, as evidenced by the delay in peritoneal absorption. Fluid removal in 6 hours should be greater when using a dialysate containing oligosaccharides such as maltotriose or maltopentaose in place of glucose.

Animals↗
PubMed1998

Can recovered protein from the CAPD patient's own dialysis effluent substitute for dextrose?

Albumin has been evaluated as an osmotic agent for peritoneal dialysis as being physiologically safe and having modest colloidal osmotic pressure. However its extremely high cost inhibits clinical applications, and hypoalbuminemia is often seen in continuous ambulatory peritoneal dialysis (CAPD) patients, especially those with high peritoneal equilibration test (PET) values and who lose a large quantity of albumin everyday. This study aims at recovering protein from CAPD effluent and reusing it safely at reasonable cost as a substitute for dextrose. The dialysis effluent was collected and concentrated with a semipermeable membrane. Uremic toxins and low-molecular-weight solutes were removed by repeated filtration and water dilution. The concentrate was acidified with hydrochloric acid down to pH 2, thence de-acidified with water dialysis up to pH 5. At this point, the isoelectric point of albumin, at which precipitate was deposited, the precipitate was separated from the supernatant and re-dissolved into electrolyte solution. The acidified concentrate exhaled an unpleasant odor, like that of decayed food. The precipitate solution, however, did not smell at all. The initial ultrafiltration rate of the recovered protein solution was measured and compared with that of dextrose and dextran by using a high-sensitivity differential manometer, one end of which was connected with the test solution cell, and the other with the serum cell. The ends were separated by a semipermeable membrane. The recovered protein solution at 20 g/dL concentration was almost equivalent in initial ultrafiltration rate to the 2.0 g/dL dextrose solution and to 20 g/dL dextran (MW: 75,000 dalton) solution.

Albumins↗
PubMed1998

In vitro and in vivo generation and kinetics of glycosylation products in peritoneal dialysis effluents.

There are indications that advanced glycosylation end-products (AGEs) may affect in some manner the functions of the peritoneum. Only a few reports discuss the actual generation of glycosylated proteins and the intraperitoneal kinetics involved during continuous ambulatory peritoneal dialysis (CAPD). To demonstrate the formation of AGEs and their time-courses in peritoneal dialysis (PD) effluents, measurements were made of furosine, carboxymethyl lysine (CML), and pentosidine as glycosylation markers in vitro and in vivo using PD effluents obtained every 2 hours for up to 8 hours from 3 nondiabetic CAPD patients. Furosine and CML were found to be generated relatively early (within 6 hours), and their de novo formation was markedly enhanced subsequent to glucose addition. Furosine and CML production increased in proportion to glucose concentration. Pentosidine production did not change with time for up to 24 hours, and was not induced by glucose during this period. Carboxymethyl lysine production appeared to be suppressed in vitro with the addition of serum protein. Furosine in the intraperitoneal dialysate was initially the same as that in the plasma, but increased to twice as much in just 2 hours in vivo. Production of CML increased, but apparently was suppressed with leakage of plasma protein into the dialysate; this possibly may have been due to dilutional or antiglycation effects in the plasma. No stimulation of pentosidine production could be detected in the intraperitoneal dialysate even at 8 hours. The initiation of glycosylation of peritoneal proteins, with generation of furosine and CML but not pentosidine, is clearly shown by the present results to occur relatively early in the intraperitoneal dialysate, i.e., within a matter of hours.

Adult↗
PubMed1998

Suppression of DNA synthesis of cultured mesothelial cells by supplemented albumin.

Mesothelial cells, harvested from rat omentum, were cultured with 10% FCS/MEM till the third passage, and then seeded at a density of 2-3 x 10(4)/cm2 in a 96 well micro-titer plate. Both albumin and glucose were added to each culture medium at final concentrations of 0-2 g/dl and 0-90 mM, respectively. On days 2 and 3, 5-bromo-2'-deoxy-uridine (BrdU) was added and incubated for 24-h to be incorporated into cellular DNA and detected by the ELISA principle. The lowest DNA synthesis was seen when both 2.0 g/dl of albumin and 90 mM of glucose were supplemented to the medium while the highest was obtained without albumin supplement. In the range of 0-90 mM of glucose and 0-2 g/dl of albumin, generally speaking, DNA synthesis of cultured mesothelial cells could be suppressed by either glucose or albumin, and it was greatly enhanced when both concentrations increased.

Albumins↗
PubMed1997

Rupture of the left main-stem bronchus by the tracheal portion of a double-lumen endobronchial tube.

We report a rupture of the left main-stem bronchus following the insertion of a left-sided double-lumen endobronchial tube in a 76-yr-old woman with a short trachea. A fiberoptic bronchoscope was not used during the initial insertion of the tube and the depth of insertion resulted in approximately 5 cm in excess of the optimal level for this patient. The rupture had been caused by the tracheal portion of the double-lumen tube. This damage may have been avoided if a fiberoptic bronchoscope was used routinely as an introducer and for positioning of the endobronchial tube under direct vision.

Adenocarcinoma↗
PubMed1997

Analysis of urinary red blood cells of healthy individuals by an automated urinary flow cytometer.

A newly developed automated urinary flow cytometer allows clear discrimination of erythrocytes from other solid components of urine. In this study, the normal range of the urinary erythrocyte count and the source of urinary erythrocytes in healthy individuals were investigated using this analyzer. For the diagnosis of the source of the urinary erythrocytes, Kitasato University Kidney Center criteria for this analyzer were applied. The subjects were 133 regularly employed volunteers (age range 20-48 years, mean 30.5) who noted no urinary tract symptoms and showed normal blood pressure, consisting of 41 females not in their menstrual period (age range 20-39 years, mean 24.8) and 92 males (age range 20-48 years, mean 33.1). Mid-stream voided urine was collected from these subjects using urine sampling cups, immediately transferred to 50-ml sterilized Spitz tubes, and analyzed within 30 min using the automated urinary flow cytometer. Urinary erythrocytes were derived from glomeruli in all samples of healthy subjects. The urinary erythrocyte count showed a logarithmic normal distribution. Values 2 SD of the urinary erythrocyte count in healthy individuals or higher were regarded as abnormal, and hematuria was considered to be positive when 11.0/microliter or more erythrocytes were observed by this analyzer. The finding by this analyzer corresponded to the report of Birch et al.

Adult↗
PubMed1997

[Effects of high fat diet and a novel antioxidant (BO653) on ischemia reperfusion injury of rat kidney].

The effect of a high fat diet (HFD) on renal function, renal mitochondrial function and intrarenal oxygen-free radial scavenging activity were examined in the ischemia-reperfusion model of the rat kidney. Whether of not a novel lipophilic antioxidant (BO653) could minimize this effect in vivo was also investigated. Thirty minutes renal ischemia was introduced by vascular clamp in rats with or without HFD (cholesterol 1.25%). Some of the HFD rats received BO653 by gastric gavage. Creatinine clearance (Ccr) was measured 24 hours following the injury. Mitochondrial oxygen consumption and thiobarbituric acid reactive substance (TBARS), superoxide dismutase (SOD), glutathione peroxidase (GPX) and alpha-tocopherol were measured in the kidney before, 30 min ischemia and 30 min after reperfusion. HFD significantly reduced Ccr after ischemia-reperfusion (45% decreased compared to normal diet), which was ameliorated by BO653. Thirty-minute ischemia deteriorated the mitochondrial function in the normal diet (ND) group, high fat diet (HFD) group and high fat diet + BO653 (HFD + BO) group. Thirty-minute reperfusion ameliorated the mitochondrial function in all those groups. The kidney content of TBARS was not increased after the ischemia-reperfusion in all these groups. In the HFD group, the kidney content of GPX was higher than in the ND group during ischemia-reperfusion, but in the HFD group, the kidney content of SOD was significantly decreased after the thirty-minute ischemia. Thirty-minute ischemia decreased the kidney content of alpha-tocopherol in the HFD group, which was recovered by the thirty-minute reperfusion. In conclusion, a high fat diet deteriorates ischemia-reperfusion injury of the rat kidney and BO653 ameliorated this effect judged by creatinine clearance and renal mitochondrial function. Reperfusion injury could not be confirmed in the present model based on the results of lipid peroxidation and oxygen-free radical scavenging enzyme activity.

Animals↗
PubMed1997

DNA synthesis of cultured mesothelial cells in a high permeable state.

To understand the mechanism of regeneration of the mesothelial cell in a high permeable state, in vitro experiments with cultured mesothelial cells were carried out using a type I collagen-coated multititer plate. Prior to cell seeding, each plate was filled with 100 microL of glucose solution at concentrations of 30 mmol/L, 90 mmol/L, and 150 mmol/L, and minimum essential medium (MEM), respectively. After immersion for one to five weeks at 37 degrees C, mesothelial cells were seeded at a density of 3 x 10(4)/cm2, then glucose was added at varying final concentrations between 0 and 150 mmol/L and/or albumin was added at a final concentration of 2 g/dL. After days 2 and 4, DNA synthesis was measured by incorporation of 5-bromo-2'-deoxy-uridine (BrdU). There was no significant difference of DNA synthesis between groups with and without one-week glucose immersion when mesothelial cells were cultured with only 10% FCS/MEM. However, suppression of DNA synthesis at 2 g/dL of albumin was seen no matter what concentration of glucose supplement was used. Without a high concentration of albumin, DNA synthesis was dose-dependent on glucose. The longer the immersion period, the lesser the suppression. It is speculated that process of glycation with collagen may relate to growth of mesothelial cells.

Albumins↗
PubMed1997

Kinetic analysis of furosine and pentosidine in CAPD patients.

Advanced glycation end products (AGEs) have been noted in the peritoneal tissue of continuous ambulatory peritoneal dialysis (CAPD) patients, and this may cause an increase in membrane permeability. In vivo and in vitro kinetic analysis was carried out on furosine and pentosidine, early and late glycation products. Plasma furosine and pentosidine were measured by HPLC in patients with renal dysfunction with or without diabetes mellitus (DM) and dialysate pentosidine and furosine in CAPD patients. Only those dialysis patients without residual renal function were used in this study. Plasma furosine was remarkably high in DM, hemodialysis (HD), and CAPD patients. Plasma pentosidine appeared to depend on renal function and was not influenced by diabetic condition. Plasma pentosidine was significantly higher in CAPD than HD patients. A weak positive correlation was noted between dialysate and plasma furosine and pentosidine, indicating the main source of furosine and pentosidine in PD effluent to be plasma. Serial dialysate sampling showed furosine and pentosidine to increase linearly. Mean dialysate/plasma (D/P) of furosine and pentosidine were 0.043 and 0.012, respectively. Protein-bound product size and in situ formation of furosine in the peritoneal cavity would be the reason for these differences in D/P. In situ formation of early glycation products in the peritoneal cavity may be concluded to take place in CAPD patients, and high plasma pentosidine may lead to its accumulation in tissue, resulting, possibly, in pathological change.

Adult↗
PubMed1997

Effects of osmotic agents on hyaluronan synthesis in human peritoneal mesothelial cells and fibroblasts.

Hyaluronan (HA) plays an important role in peritoneal tissue remodeling and the inflammatory process. In this study, attention was directed to the effects of various osmotic agents on HA synthesis in human peritoneal mesothelial cells (HMCs) and fibroblasts (HFBs). Following incubation with growth arrest media for 48 hours, the cells (4 x 10(4)/mL) were incubated for 72 hours in media at various concentrations (50, 100 mmol/L for crystalloid agents and 3.5%, 7% for oncotic agents) of glucose, mannitol, glycerol, sucrose, raffinose, NaCl, combined amino acids, maltodextrin, dextran 70, and hydroxyethylstarch 20. HA synthesis for 72 hours was measured by sandwich-binding protein assay. HMCs synthesized approximately 0.15 ng/cell/72 hours and HFBs 0.09 ng. All crystalloid osmotic agents significantly suppressed HA synthesis by HMCs and HFBs in a concentration-dependent manner. There was no such suppression by any oncotic osmotic agent, which, to the contrary, enhanced the synthesis by 6%-63% in HMCs. In conclusion, HMCs and HFBs may be considered sources of HA in the peritoneal dialysis effluent. Crystalloid osmotic agents suppressed HA synthesis in these cells. Oncotic osmotic agents seem to be less toxic in this regard.

Amino Acids, Essential↗
PubMed1997

Prognosis for patients with sclerosing encapsulating peritonitis following CAPD.

Sclerosing encapsulating peritonitis (SEP) is a very serious complication of CAPD. The present study was conducted on 7 SEP patients (4 male, 3 female, average age 33 years) from among 197 continuous ambulatory peritoneal dialysis (CAPD) patients over a period of 14 years. SEP affected 3.7% (7/197) of the CAPD patients in this study, and its annual incidence was found to be 2.6/1000. All 7 patients in this study exhibited ileus. The 3 patients with severe peritonitis and sepsis had transient ileus. The prognosis was poor for 3 patients who reported prior ultrafiltration problems. One of these patients died one year after the onset of SEP. The prognosis for one of the patients showed an intermediate course. SEP patients may possibly be divided into subgroups based on the course of prognosis. SEP patients with previous UF failure and longer duration of CAPD showed poorer prognoses. The quality of life, especially in regard to eating, is poor.

Adolescent↗
PubMed1996

Effects of osmotic solutes on fibronectin mRNA expression in rat peritoneal mesothelial cells.

Hypertonic glucose in a peritoneal dialysate may modulate cell metabolism in the peritoneal cavity during continuous ambulatory peritoneal dialysis (CAPD). To examine the effects of high glucose concentration and hyperosmolarity, rat mesothelial cells were cultured for 3 or 6 days in media containing either 5, 25 or 50 mM glucose containing 20 or 45 mM mannitol. Fibronectin gene expression was investigated by Northern blot analysis. By day 6, fibronectin mRNA levels increased compared to 5 mM glucose controls with increasing glucose concentration (25 mM, 193%, 50 mM, 314%); high osmolarity due to mannitol did not increase mRNA levels (20 mM and 45 mM mannitol yielded 75 and 104%, respectively). Thus, hypertonic glucose augments fibronectin gene expression in peritoneal mesothelial cells due to the higher concentrations of glucose and not to hyperosmolarity. The glucose-driven increase in fibronectin expression may contribute to the peritoneal fibrosis in CAPD patients.

Animals↗