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Biomedical subjects

C Higuchi

Publications and source records attributed to C Higuchi.

At least 19 recordsLinked to original sources
PubMed2006

Surgical outcomes after treatment of fractures in femur and tibia in pycnodysostosis.

Pycnodysostosis is a rare hereditary disease, characterized by systemic bone sclerosis. The most important orthopedic problem in this condition is the recurrent pathological fracture of long bones. In this paper, the surgical results for fractures of six limbs (three femurs and three tibias) in five cases of pycnodysostosis are reported. Five limbs achieved fracture union and union is developing in one tibia after intramedullary nail (IM) nailing or Ilizarov external fixation (IEF), although fracture line tends to persist for longer periods of time. One femoral fracture was treated by IM nailing, and one femoral and one tibial fracture were treated by IEF leading to final bone union. One femoral and one tibial fracture were initially treated by IEF, and were treated by IM nailing after re-fracture. One tibial fracture was initially treated by IEF leading to a failure of union, and was converted to IM nailing. All cases are able to walk; one case requires a single crutch. Infection was noted in two limbs after IM nailing following IEF. Fixation with IM nail was effective in preventing re-fracture as well as in alignment correction. Although the surgical technique is more difficult, IM nailing in the initial surgery may be a better choice for achieving successful union while reducing the risk of re-fracture or infection.

Adult↗
PubMed2003

Expression and distribution of transcripts for sonic hedgehog in the early phase of fracture repair.

Localization and expression of mRNAs for sonic hedgehog (Shh) at a fracture site in the early phase postfracture were investigated by in situ hybridization and reverse transcription and polymerase chain reaction (RT-PCR). A closed fracture was made in the midshaft of the right tibia of 5-week-old ICR mice, and fractured sites were harvested prefracture (day 0) and on days 2 and 12. In situ hybridization revealed that transcripts for Shh were not detected on day 0, but they were detected in proliferating callus-forming cells in the periosteum and the surrounding tissue, and in the medullary cavity prior to apparent new cartilage and bone formation. Gli 1 (a signaling mediator for Shh) and bone morphogenetic protein-4 transcripts were colocalized with those for Shh transcripts on day 2. The RT-PCR showed that Shh mRNA was detected in the PCR product from day 2, but not from days 0 and 12. These findings are the first description about the activation of Shh gene in the early postfracture reaction.

Animals↗
PubMed2000

Neutrophil activation in immunoadsorption.

Immunoadsorption therapy (IAT) is used in the treatment of autoimmune diseases. Although IAT has been reported to modify humoral immunity by inducing chemokines and activating complements, much remains unknown about the biological effects of IAT on cellular components in peripheral blood. To define the influence of IAT on leukocytes, we determined leukocyte L-selectin (CD62L) and Mac-1 (CD11b) as parameters for activation of leukocytes in peripheral blood during IAT. Peripheral leukocyte L-selectin and Mac-1 were determined continuously by flow cytometry in 6 patients with neuroimmunological disorders in whom IAT was conducted using a Plasma Flow OP-05 (Asahi Medical Corp., Tokyo, Japan) as a plasma separator and Immusorba TR-350 (Asahi Medical Corp., Tokyo, Japan) as an adsorption column. Expression of neutrophils (PMN) L-selectin was decreased 30 min after starting IAT, with the decreases particularly marked at the end of IAT, while expression of mononuclear cells (MNC) L-selectin slightly increased during IAT. Expression of PMN Mac-1 was markedly increased at the end of IAT, whereas expression of MNC Mac-1 did not change during IAT. Leukocyte counts decreased 30 min after starting IAT, and then increased to the initial level or higher in parallel with L-selectin downregulation and Mac-1 upregulation on PMN. L-selectin downregulation and Mac-1 upregulation on PMN suggested that activation of PMN associated with changes in peripheral leukocyte counts occurred during IAT and might play some role in modulating the human circulating blood and immune systems.

Adolescent↗
PubMed2000

Reduction of neutrophil activation by vitamin E modified dialyzer membranes.

BACKGROUND/AIM: Transient leukopenia during hemodialysis due to neutrophil activation is attributed to bioincompatibility of the dialysis membrane, but the mechanism remains unclear. We studied the mechanism of neutrophilic activation by comparing a vitamin E modified membrane (CLEE) and a regular cellulose membrane (CLSS). METHODS: (1) CLSS and CLEE membranes were used in a crossover clinical study in 7 chronic hemodialysis patients. Neutropenia, CD11b expression, and plasma C3a and myeloperoxidase concentrations were compared between the two dialyzer membranes. (2) Normal blood was circulated through CLEE and CLSS minimodels, and the same parameters were compared. (3) Blood samples with modified complement activities (EDTA: both classical and alternative pathways inactivated; EGTA+Mg: classical pathway inactivated; heating: alternative pathway inactivated; control: no modification) were incubated in the CLSS minimodel, and the neutrophilic activation was compared. RESULTS: In clinical hemodialysis, neutropenia, CD11b expression, and C3a and myeloperoxidase levels were significantly lower when CLEE membranes were used. The same tendency was observed in minimodels. However, the degrees of inhibition in clinical dialysis, especially at the venous line, were significantly higher than in minimodels. As compared with controls, CD11b expression and myeloperoxidase level were significantly lower when both classical and alternative pathways were inactivated or when the classical pathway alone was inactivated, but were not significantly different when the alternative pathway alone was inactivated. CONCLUSIONS: Vitamin E modification of the dialyzer reduces some reactions of neutrophilic activation, such as CD11b expression and myeloperoxidase release, more effectively in the clinical situation than in ex vivo models, suggesting a possible effect of vitamin E in inhibiting bioreactions due to pyrogen in the dialysate. The classical complement pathway is required in membrane-induced neutrophilic activation, at least during the initial stage.

Adult↗
PubMed1999

The role of protein kinase C activity in the proliferation of peritoneal fibroblasts.

OBJECTIVE: To clarify the effect of glucose on peritoneal sclerosis, we performed several experiments to determine how glucose influences the proliferation of, and the production of extracellular matrix proteins by, peritoneal fibroblasts. The effect of heparin on these phenomena was also studied. DESIGN: Using rat peritoneal fibroblasts, cells were cultured in four separate media: M199 with 5% fetal bovine serum (FBS) (control medium), control medium with 4% glucose (glucose medium), glucose medium with H7 [an inhibitor of protein kinase C (PKC)] 50 micromol, and glucose medium with heparin 50 microg/mL. Cell proliferation and concentrations of procollagen 3 peptide (P3P) and hyaluronic acid (HA) in the supernatants were evaluated at 24 hours, 72 hours, and 120 hours after culture. PKC activity in cytosolic and cell membrane fractions were measured 30 minutes after incubation in control medium and in glucose medium with and without heparin. RESULTS: Glucose accelerated cell proliferation 24 hours after culture, but inhibited it 120 hours after culture. Glucose stimulated the production of HA from these cells 72 hours and 120 hours after culture, but it did not stimulate the production of P3P at any time. Heparin and H7 inhibited cell proliferation by glucose 24 hours after culture. Heparin and H7 also inhibited the production of HA in the peritoneal fibroblasts after culture, but did not affect the production of P3P. Glucose accelerated PKC activity in cell membrane, but not in cytosol. Heparin inhibited the elevated PKC activity of the membrane fraction by glucose. CONCLUSION: Glucose may accelerate the proliferation of, and HA production in, peritoneal fibroblasts by stimulation of cellular PKC activity. Heparin suppresses these phenomena by inhibiting PKC activity.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1997

Down-regulation of manganese-superoxide dismutase gene expression in idiopathic nephrotic syndrome.

An oxidant stress has been shown to prevail in experimental and clinical nephrotic syndrome. Such oxidant stress may be induced by a reduced activity of antioxidant systems. We examined the altered expression of manganese-superoxide dismutase (Mn-SOD), an antioxidant enzyme, in patients with idiopathic nephrotic syndrome, in whom an increased oxidant stress had been demonstrated. The Mn-SOD activities in peripheral blood mononuclear cells obtained from 12 patients with active nephrotic syndrome (6.0 +/- 1.1 years of age, mean +/- SE) and hypoproteinemia were 42% lower (p < 0.05) than in 12 control subjects (5.5 +/- 0.5 years of age) with normal serum total protein concentrations. Reverse-transcriptase polymerase chain reaction also demonstrated that Mn-SOD messenger RNA expression in the patients with nephrotic syndrome was, on average, 59% lower than in control subjects. Because expressions of some genes are sensitive to serum, the serum dependency of Mn-SOD gene transcription was studied in glomerular endothelial cells transfected with a luciferase reporter gene fused with a rat Mn-SOD DNA fragment of -806 to +22 bp of the transcription initiation site (-806:+22). When these cells were exposed to different concentrations of fetal bovine serum (0.5% to 15%), the transcriptional activities determined by luciferase activities were proportional to serum concentrations. This serum-dependent transcriptional activation was also demonstrated by the fragment (-220:+22) but not by the fragment (-220:-20). When glomerular endothelial cells transfected with the fragment (-220:+22) were treated with 5% serum from patients with active nephrotic syndrome, transcriptional activation was more than 80% less than that by 5% serum from control subjects without nephrosis. These results indicate that Mn-SOD gene transcription is regulated at least in part by serum, and that the serum-dependent transcription of the gene is diminished in patients with idiopathic nephrotic syndrome. The regulatory region of serum-dependent gene transcription resides within its early promoter region. Our findings suggest that down-regulation of antioxidant enzyme transcription may contribute increased oxidant stress in idiopathic nephrotic syndrome.

Animals↗
PubMed1997

Therapeutic effect of a newly developed antioxidative agent (OPC-15161) on experimental immune complex nephritis.

The effect of a newly developed free radical scavenger (OPC-15161) on the progression of nephrotoxic serum (NTS) nephritis was evaluated. NTS nephritis rats were sacrificed immediately before and 1, 2, 3, 6, and 24 h and 13 and 19 days after intravenous injection of NTS. The tissue content of phosphatidylcholine hydroperoxide, the activity of superoxide, the activity of superoxide dismutase in the renal cortex, and the serum malondialdehyde levels were measured. The phosphatidylcholine hydroperoxide content in the renal cortex of OPC-15161-treated NTS nephritis rats was lower than that in the control rats 24 h after NTS injection. The activity of superoxide dismutase in OPC-15161-treated rats was sustained in contrast to the decrease in this activity in the control rats 6 h after injection of NTS. The effects of OPC-15161, dipyridamole, and prednisolone on NTS nephritis rats were investigated. OPC-15161 (20 mg/kg p.o.) showed a potent inhibitory effect on the urinary protein excretion, whereas dipyridamole (30 and 100 mg/kg p.o.) and prednisolone (2 mg/kg p.o.) had less suppressive effects. In view of these results, we conclude that OPC-15161 notably ameliorated the urinary protein excretion by way of the suppression of lipid peroxidation in the renal tissue of NTS nephritis rats.

Animals↗
PubMed1997

The effect of glucose on the proliferation of peritoneal fibroblasts.

The purpose of this study was to clarify the pathophysiological role of glucose and glucose transporters (GLUTs) in the proliferation and production of extracellular matrix (ECM) in peritoneal fibroblasts. Peritoneal fibroblasts from rat omentum were cultured in medium M199 with 5% fetal bovine serum (FBS) with (Group B) and without (Group A) 4% glucose. The rate of cell growth at the M stage of the cell cycle in Group B was higher than that in Group A at 12 and 24 hours after culture. However, cell numbers in Group B were less than in Group A at 24, 72, and 120 hours after culture. The GLUT inhibitor suppressed the proliferation of cells 72 and 120 hours after culture. The procollagen III peptide (PIIIP) contents in the supernatant of cells cultured in a high glucose medium were higher than those of control cells at 24, 72, and 120 hours after culture. PIIIP levels of cells cultured with the GLUT inhibitor were also higher than those of cells without the GLUT inhibitor. These results suggest that initially glucose stimulates cell proliferation and thereafter inhibits its proliferation. GLUTs may accelerate the proliferation of peritoneal fibroblasts. We suggest that glucose stimulates the ECM component PIIIP, and GLUT may have an inhibitory effect on the production of the ECM component PIIIP.

Animals↗
PubMed1995

Lipid peroxidation as an indicator of biocompatibility in haemodialysis.

Peroxidation of cell membrane (phosphatidylcholine hydroperoxide, PCOOH) was quantitatively assessed using a chemiluminescence-HPLC system to clarify whether haemodialysis patients are damaged by oxidative stress. Patients were divided into two groups, one dialysed with conventional cellulose membranes, and the other with cellulose triacetate for 3 months, subsequently followed by a crossover study of each membrane for 3 more months. The mean value of PCOOH in haemodialysis patients was 508.5 +/- 208.7 pmol/ml (P < 0.01 vs normal controls), which showed a statistically insignificant tendency to increase during each haemodialysis session of 4 h. Two years after commencing haemodialysis, PCOOH was maintained within almost the same range, but significantly greater than normal. There was no significant tendency between an index of aortic sclerosis and plasma PCOOH. However, three patients using conventional cellulose membranes died of myocardial infarction. Plasma PCOOH increased after the commencement of haemodialysis. This tendency was more notable in patients using conventional cellulose membrane compared to the cellulose triacetate. Cellulose triacetate, which we thought to be more biocompatible, did not necessarily produce lipid peroxide. We conclude that it is very important to check production of oxygen radicals when developing new membranes.

Biocompatible Materials↗
PubMed1995

Immunotherapy with interleukin 2 with or without lymphokine-activated killer cells after autologous bone marrow transplantation for malignant lymphoma: a feasibility trial.

Early relapse remains a major challenge after autologous bone marrow transplant for malignant lymphoma (ML). It is postulated that consolidative immunotherapy with interleukin 2 (IL-2) with or without lymphokine-activated killer (LAK) cells administered after autologous bone marrow (ABMT) or peripheral blood stem cell transplantation (PBSCT) for ML might eradicate residual disease and reduce relapse rates. A previous trial identified an IL-2 regimen that could be administered early after ABMT. This paper presents the clinical results of 16 patients with ML, who participated in a study to determine whether LAK cells could be administered after ABMT with this IL-2 regimen, as well as 6 patients who received IL-2 alone after ABMT or PBSCT. Seventeen patients with non-Hodgkin's lymphoma (NHL), and 5 with Hodgkin's disease (HD), underwent ABMT (20 patients) or PBSCT (2 patients). At the time of transplantation, 7 patients were in untreated or chemotherapy-sensitive first relapse, 3 were in CR2, and 12 were beyond CR2. Beginning 22-85 days (median 43) after ABMT/PBSCT, patients received IL-2 at 3.0 x 10(6) U/m2/day by continuous infusion days 1-5 of the IL-2 protocol. On protocol days 7-9 the first 16 patients underwent apheresis for LAK cell generation. The cells were cultured in IL-2 for 5 days and were infused on days 12-14. Low-dose IL-2 (0.9 x 10(6) IU/m2/day) was administered on days 12-21 in the outpatient department. Patients received a median of 148 (62-279) x 10(9) LAK cells. LAK cell infusions were associated with transient fevers, chills and dyspnea in most patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Accumulation of phosphatydilcholine-hydroperoxide in dialysis patients with diabetic nephropathy.

Plasma lipid peroxidation in noninsulin dependent diabetes mellitus (DM) patients were evaluated in DM patients undergoing hemodialysis (HD) by means of a chemiluminescence-HPLC for the specific determination of phosphatidylcholine hydroperoxide (PCOOH). Thirty-three uremic patients with DM nephropathy, undergoing 12 hours HD a week using polymethylmethacrylate membrane, were studied. Of them 22 DM patients on HD were divided into 2 age and sex matched groups treated and conventional group in order to clarify therapeutic effect of 500 mg alfa-tocopherol and 600 mg probucol daily. Fifty DM patients without end-stage renal disease (ESRD) who were age-, period of diabetes-, and sex-matched, were selected as positive control of the subjects. Plasma PCOOH levels were significantly elevated in both DM patients, while the plasma PCOOH in normal controls were 227.0 +/- 68.7 pmol/ml. Plasma PCOOH levels of DM patients undergoing HD were significantly higher than that of patients without ESRD (1,330.8 +/- 642.7 pmol/ml vs. 756.6 +/- 431.9 pmol/ml, p < 0.025). Partial correlation coefficient of plasma PCOOH level demonstrated PCOOH and period of HD in DM patients were highly significantly positively correlated (p < 0.01), although single session of HD was not found to produce significantly increased lipid-peroxidation. Plasma PCOOH roughly remained within similar levels as base lines by medication with anti-oxidant compared to that of conventional group. From these results we conclude that HD intensifies lipid peroxidation and such accumulation of hydroperoxide could account for accelerated progress of atherosclerosis in DM patients with renal insufficiency. It is worthwhile to try an administration of free radical scavenger in order to reduce PCOOH and slow down the progression of atherosclerotic vascular disease.

Adult↗
PubMed1993

Interleukin-2 +/- lymphocytes as consolidative immunotherapy after autologous bone marrow transplantation for hematologic malignancies.

Patients who undergo autologous bone marrow transplantation (ABMT) for advanced hematologic malignancies experience a high relapse rate. Therapy with interleukin-2 (IL-2) +/- lymphokine-activated killer (LAK) cells has induced clinical responses in some patients with advanced malignant lymphoma (ML) or acute myelogenous leukemia (AML). It is postulated that IL-2 +/- LAK cells represents a potentially non-cross-resistant therapeutic modality which might prevent or delay relapses if used as consolidative immunotherapy after ABMT, at a time of minimal residual disease. Therefore, we first studied the reconstitution of IL-2-responsive LAK precursor cells after ABMT and found them in the circulation as early as 3 weeks after ABMT. A phase Ib clinical trial was then performed which identified a tolerable IL-2 regimen which could be administered early after ABMT and which could induce immunomodulatory effects. We then initiated a clinical trial to determine the feasibility of generating and administering autologous LAK cells using this IL-2 regimen after ABMT for 16 patients with ML. The results show that IL-2+LAK therapy early after ABMT is feasible but is more toxic than IL-2 alone. Patients with AML on the phase I IL-2 trial and with ML on the IL-2+LAK protocol were evaluated for tumor status. Of 8 patients with AML in first relapse or at a later stage who underwent ABMT and received IL-2, 2 have relapsed, while 6 remain in complete remission 26+ to 40+ (median 28+) months after ABMT. Of 16 patients with ML considered at high risk for relapse who were treated with ABMT+IL-2+LAK, 5 have relapsed, while 11 remain in complete remission at 6+ to 21+ (median 10+) months after ABMT. The results in both trials are quite encouraging and appear to be better than those in nonrandomized historical controls at our institution. Prospectively randomized trials of IL-2 versus no IL-2 after ABMT in such patients are being initiated to assess definitively the effect, if any, on the relapse rate.

Bone Marrow Transplantation↗
PubMed1993

[Success of cyclosporine therapy in two patients with PSS].

Two PSS patients, unresponsive to D-penicillamine, steroid, cyclophosphamide and plasma exchange therapy, were treated with cyclosporine. One patient complained scleroderma, dysphagia and dyspnea during movement after treatment with steroid, plasma exchange and cyclophosphamide. He showed a increased Leu3a/2a ratio (6.72). About 3 months after treatment with cyclosporine, these complain decreased with normalization of elevated Leu 3 a/2 a ratio. 1 year after treatment, %DLco increased 86% from 50% and pneumonitis findings of chest X-ray and chest CT were also improved. Another patient who complained Raynaud's phenomenon and scleroderma which had extended over his abdomen despite treatment with steroid and cyclophosphamide. 1 month after treatment with cyclosporine, improvement of these phenomenon were recognized. It is concluded that cyclosporine can be an effective agent in the treatment of PSS.

Cyclosporine↗
PubMed1989

[Pathophysiological mechanism of ischemic acute renal failure: protective effect of coenzyme Q10, Ca channel blocker, superoxide dismutase and protease inhibitor against ischemic acute renal failure].

Ischemic insult has been considered a cause of cellular injuries under certain circumstance, such as the disturbance of energy metabolism, the alternation of calcium homeostasis, the production of oxygen radical and the release of lysosomal protease. The present study was designed to clarify the pathophysiological effects of coenzyme Q10 (CoQ10), diltiazem, superoxide dismutase (SOD) and urinastatin on the development and progression of ischemic acute renal failure (IARF) of the rat. At 24 hours after reflow following 45 minutes ischemia, serum urea nitrogen, creatinine and fractional excretion of sodium were 99.3 mg/dl, 3.14 mg/dl, 5.95% respectively, in non-treated IARF rats. Renal ATP content was reduced to 0.91 micrograms/mg. prot. from 10.59 micrograms/mg. prot. at 10 minutes after ischemic insult, and remained at almost the same level throughout the entire 45 minutes ischemia. Although the subsequent blood reflow resulted in the recovery of ATP content, it was up to 50% of normal level at 24 hours after reflow following 45 minutes ischemia. During the ischemic period, the pathological changes were mild, whereas, after reflow, tissue involvement was mainly localized in the S3 segment of the proximal tubule. Major alteration were the loss of brush border, high amplitude swelling of mitochondria with matrical densities and fragmentation of the epithelial cell. At 24 hours after reflow, it was observed that renal function was superior in IARF rats treated with CoQ10, diltiazem, SOD and urinastatin. The treated rats also had higher ATP contents and showed less pathological changes than non-treated rats. Among these inhibitory agents, diltiazem exerted the most reliable effect. From these results, it was concluded that IARF was obviously caused by such pathophysiological mechanisms as mentioned above. Especially, Ca influx into the cells is one of the most important factors on pathogenesis of IARF.

Acute Kidney Injury↗