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K Naito

Publications and source records attributed to K Naito.

At least 73 records · Page 4Linked to original sources
PubMed2001

All-trans retinoic acid (ATRA) differentiates acute promyelocytic leukemia cells independently of P-glycoprotein (P-gp) related multidrug resistance.

Here the relationship between all-trans retinoic acid (ATRA)-resistance and P-glycoprotein (P-gp)-associated multidrug resistance (MDR) is discussed in acute promyelocytic leukemia (APL). First, the remission rates of ATRA therapy are similar in relapsed/refractory APL to the preceding chemotherapy given and in newly diagnosed APL. Second, MDR1 cDNA-transduced NB4 (NB4/MDR) cells accumulate less Rhodamine-123 (Rh123) than NB4 cells, but there is no difference in the intracellular ATRA concentration between them. PSC833 or MS209. MDR modifiers, increases the intracellular accumulation of Rh123 in NB4/MDR and APL cells expressing P-gp, but not of ATRA. Third, the expression of CD11b, the NBT reduction activity, the proportion of apoptotic cells and the morphology are not different between NB4/MDR and NB4 cells, and between APL cells expressing P-gp and not. APL cells express little P-gp, and mainly express CD33 but no CD34. Despite previous reports that ATRA-resistant APL cells express more P-gp than ATRA-sensitive ones, P-gp and ATRA-resistance seems to exist independently.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

[A case of infected urachal cyst successfully drained by a catheter perforating the bladder].

A 42-year-old man complained of lower abdominal pain. Computed tomographic scan and magnetic resonance imaging revealed an infected urachal cyst. A drainage catheter, which had multiple holes over a 10 cm length from the catheter tip, was placed in the urachal cyst. The catheter was inserted from the subumbilicus region and the catheter tip was intended to be situated at the caudal end of the urachal cyst. However, the catheter tip accidentally perforated the bladder and urine flowed out of the bladder through the catheter. Because the urine diluted and washed out the pus in the urachal cyst, the infected urachal cyst was successfully drained. Percutaneous drainage and antibiotics allowed resolution of the inflammatory process. On the twenty-third day after catheter placement, excision of the urachal cyst and partial cystectomy were performed with relative ease and without any complications.

Adult↗
PubMed2001

[Successful treatment using iron depletion phlebotomy combined with recombinant erythropoietin after allogeneic bone marrow transplantation for myelodysplastic syndrome complicated by secondary hemochromatosis].

A 33 year-old female patient presented with apparent skin pigmentation, sustained liver dysfunction and impaired glucose tolerance. She had received blood transfusions totalling more than 40,000 ml for myelodysplastic syndrome and an allogeneic bone marrow transplant from her HLA-matched sister at the age of 31. Ferrokinetic data showed a significant iron overload. Magnetic resonance imaging suggested excessive iron deposition in the liver. The patient was diagnosed as having secondary hemochromatosis. She was given subcutaneous injections of 6,000 units of recombinant human erythropoietin initially twice a week and then weekly, and phlebotomies were performed to maintain her hemoglobin level above 10 g/dl. Three years later, the total volume of phlebotomized blood reached 24,000 ml, and her ferrokinetic data, serum transaminase levels, glucose tolerance and skin color were significantly improved.

Adult↗
PubMed2001

Vasectomy impairs spermatogenesis through germ cell apoptosis mediated by the p53-Bax pathway in rats.

PURPOSE: The pathophysiology of impaired spermatogenesis after vasectomy has not been completely investigated. We examined the role of p53 protein in cell cycle arrest and apoptosis of germ cells after vasectomy in the rat. MATERIALS AND METHODS: Eight-week old rats underwent bilateral vasectomy and the testes were harvested 1, 4, 8, 12 and 24 weeks after surgery. Germ cell apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) and electrophoresis assay of DNA fragmentation. Western blot analysis and immunohistochemistry were performed to examine the expression of p53, proliferating cell nuclear antigen, Bax, Bcl-2, p21WAF1/Cip1 and Gadd45. To evaluate spermatogenesis, testicular weight and percent of haploid cells flow cytometry was done. RESULTS: Spermatogenesis impairment was associated with increased p53 and decreased proliferating cell nuclear antigen expression at the delayed phase more than 8 weeks after vasectomy. The number of TUNEL positive germ cells was increased at the early 1-week and delayed phases after vasectomy. Bax but not p21WAF1/Cip1 or Gadd45 expression was increased. p53, Bax and TUNEL positive cells were co-localized in the seminiferous tubules. CONCLUSIONS: Spermatogenesis was impaired after vasectomy by apoptosis but not by cell cycle arrest. The p53-Bax pathway effects apoptosis in the delayed phase after vasectomy in some seminiferous tubules.

Animals↗
PubMed2001

Deletions on chromosome 8p22 may predict disease progression as well as pathological staging in prostate cancer.

PURPOSE: A recent report demonstrated that the deletion of chromosome 8p22 could predict disease progression in stage III (capsular penetrating) prostate cancer. We studied if the status of chromosomal deletions of 8p22 could reflect pathological stage as well as patient prognosis, thereby serving as a diagnostic tool to optimize the treatment strategy in prostate cancer. EXPERIMENTAL DESIGN: A total of 97 patients (41 Japanese and 56 Swedish) were studied by the fluorescence in situ hybridization technique. Seventy-seven patients (23 pT2, 18 pT3, and 36 pN+ tumors) underwent surgery (radical prostatectomy or lymph node dissection). The specimens were prepared by touch biopsy. From another 20 cases, fine-needle aspiration biopsies were obtained. RESULTS: 8p22 deletions were detected in 47 (61%) and 11 (55%) specimens of 77 touch biopsies and 20 fine-needle aspiration biopsies, respectively. No significant difference was found in the frequency of 8p22 deletion between different preparations of specimens, as well as between different races (Japanese versus Swedish). The frequency of 8p22 deletion was statistically higher in patients with pT3 or more than in those with pT2 (P < 0.01). Disease progression was evaluated in 57 patients. The Cox proportional hazards model revealed 8p22 deletion to be the strongest parameter to predict disease progression (hazards ratio = 5.75; P = 0.0001). CONCLUSIONS: Studies on chromosomal deletions of 8p22 by fluorescence in situ hybridization technique may serve as a genetic marker to optimize the treatment strategy in patients with prostate cancer to the optimal treatment.

Aged↗
PubMed2001

[Laparoscopic salvage of malfunctioning peritoneal dialysis catheters caused by ovarian fimbria: a case report].

We report a case of peritoneal dialysis catheter obstruction caused by ovarian fimbria, which was successfully treated with laparoscopic surgery. In June 2000, a 51-year-old woman, who started peritoneal dialysis in April 2000, complained of outflow obstruction of peritoneal dialysis fluid. Fluoroscopic imaging demonstrated the obstruction of peritoneal dialysis catheter by ovarian fimbria. Since the alpha technique under the fluoroscopic imaging did not improve the obstruction, the ovarian fimbria was removed laparoscopically in June 5, 2000. Peritoneal dialysis was successfully started the day after the surgery with no leakage of peritoneal dialysis fluid. The patient has remained without obstruction of peritoneal dialysis catheter for 8 months postoperatively.

Catheters, Indwelling↗
PubMed2000

Prolongation of the QT interval and ventricular tachycardia in patients treated with arsenic trioxide for acute promyelocytic leukemia.

BACKGROUND: Recently, arsenic trioxide has increasingly been used for relapsed acute promyelocytic leukemia. However, it is known to have several adverse effects, including acute cardiac toxicities. OBJECTIVE: To determine cardiac toxicities resulting from arsenic trioxide therapy in patients with relapsed or refractory acute promyelocytic leukemia. DESIGN: Phase II clinical prospective cohort study. SETTING: A university hospital in Hamamatsu, Japan. PATIENTS: 8 patients with relapsed acute promyelocytic leukemia. INTERVENTION: Arsenic trioxide, 0.15 mg/kg of body weight, administered daily by 2-hour infusion for a maximum of 60 days. MEASUREMENTS: Continuous monitoring with ambulatory electrocardiography. RESULTS: Five patients (63%) achieved complete remission. During induction therapy with arsenic trioxide, prolonged QT intervals were observed in all patients. Ventricular premature contractions were noticed during 8 of 12 courses of therapy. Four patients developed nonsustained ventricular tachycardia and required treatment with antiarrhythmic agents. CONCLUSIONS: Cardiac toxicity occurs during arsenic trioxide therapy in patients with acute promyelocytic leukemia. Such patients should be monitored for prolonged QT intervals and ventricular arrhythmia.

Adult↗
PubMed2000

Expression of myostatin gene in regenerating skeletal muscle of the rat and its localization.

The expression of myostatin mRNA was examined in regenerating skeletal muscle of the rat. Skeletal muscle regeneration was induced by injecting bupivacaine or hypertonic saline solution into the femoral muscle, and the tissues were collected 48 h after the treatment. In situ hybridization analysis revealed that the cells positive for myostatin message were localized in the regenerating area of the bupivacaine-treated tissues, where a numerous number of mononucleated cells were present. The myostatin-positive mononucleated cells contained both myogenic and nonmyogenic cells, as revealed by immunohistochemical staining for desmin and vimentin. Bupivacaine treatment to the testes resulted in no myostatin message expression in the testicular vimentin-positive cells, suggesting that the expression of myostatin message in vimentin-positive cells is a skeletal muscle-specific phenomenon. Furthermore, crushed muscle extract prepared from regenerating skeletal muscle had induced myostatin mRNA expression in skeletal muscle-derived fibroblasts in a dose-dependent manner. These results indicated that myostatin is expressed during skeletal muscle regeneration both in myogenic and nonmyogenic cells, and suggested that some factor(s) capable of inducing myostatin expression in fibroblasts are present in regenerating skeletal muscle.

Animals↗
PubMed2000

Establishment of fetal gonad/mesonephros coculture system using EGFP transgenic mice.

In developing mouse embryos, the Sertoli cells, Leydig cells, and seminiferous cords are differentiated in the XY gonads. The migration of mesonephric cells into the gonads is required during the developmental stage for seminiferous cord formation in the male gonads. In previous experiments, an organ coculture system has been used to examine morphologically developing gonads. However, by the process used in this system for fixing and staining the gonad/mesonephros complexes for examination, the kinetics of cell migration and the character of migrating cells cannot be observed. In the present study, we established an improved organ coculture system, using transgenic mice ubiquitously expressing Enhanced Green Fluorescent Protein (EGFP). In this system, time-dependent morphological changes in male-specific migration were observable in the gonad/mesonephros complex. The cell migration occurred at around 20 hr of coculture and began to spread at 25 hr with increases in the number of migrating cells occurring at 45 hr of coculture. No degenerative changes were detected at the end of coculture. Our results indicate that the present coculture system is very useful for investigating the mechanism of cell migration, as well as the characteristics of the migrating cells, in developing gonads. J. Exp. Zool. 286:320-327, 2000.

Animals↗
PubMed2000

Ulinastatin attenuates reperfusion injury in the isolated blood-perfused rabbit heart.

BACKGROUND: Ventricular dysfunction after long cardioplegic arrest has been observed in cardiac operations. Urinary trypsin inhibitor, also called ulinastatin, may attenuate myocardial ischemia-reperfusion injury. The present study was designed to determine the protective efficacy of ulinastatin in blood-perfused parabiotic isolated rabbit hearts as a surgically relevant model with long (4-hour) cardioplegic arrest. METHODS: Each isolated rabbit heart, with a latex balloon inserted in the left ventricle, was parabiotically blood-perfused using a modified Langendorff column. The left ventricular developed pressure, rate of pressure development, and coronary flow with a left ventricular end-diastolic pressure of 10 mm Hg were measured before ischemia and 15, 30, 45, and 60 minutes after reperfusion began (control, n = 10). Ulinastatin (15,000 U/kg) was administered to the support animal just before reperfusion began (group U-1, n = 10) or at the beginning of the extracorporeal circulation and readministered before reperfusion (group U-2, n = 10). The endothelium of the coronary artery was observed by scanning electron microscopy to evaluate the extent of endothelial ischemia-reperfusion injury. RESULTS: Ulinastatin enhanced the recovery of developed pressure in both the U-1 (p<0.05) and U-2 (p < 0.01) groups compared with the control group. Although ulinastatin given just before reperfusion (group U-1) did not enhance the recovery of the rate of pressure development or the coronary flow compared with the control, earlier administration did improve the recovery of the rate of pressure development compared with the control (U-2, p<0.05), and there was improvement of the recovery of coronary flow after 60 minutes of reperfusion (U-2, p<0.05). Scanning electron microscopy showed that ulinastatin had ameliorated coronary endothelial damage. CONCLUSIONS: Ulinastatin improved functional recovery after long cardioplegic arrest and reduced coronary endothelial injury. Administration of ulinastatin at the beginning of cardiopulmonary bypass and just before reperfusion may be useful clinically in cases requiring prolonged aortic cross-clamping.

Animals↗
PubMed2000

Leukocyte-depleted reperfusion after long cardioplegic arrest attenuates ischemia-reperfusion injury of the coronary endothelium and myocardium in rabbit hearts.

OBJECTIVE: Cardiopulmonary bypass activates leukocytes, which should injure the coronary endothelium and myocardium during reperfusion especially after long cardioplegic arrest with long cardiopulmonary bypass time. The present study was designed to determine the protective efficacy of leukocyte-depleted reperfusion in blood-perfused parabiotic isolated rabbit hearts as a surgically relevant model with long cardioplegic arrest. METHODS: Each isolated rabbit heart, with a latex balloon inserted in the left ventricle, was parabiotically blood-perfused using a modified Langendorff column. The left ventricular developed pressure (DP), rate of pressure development (dP/dT), and coronary flow with a left ventricular end-diastolic pressure of 10 mmHg were measured before ischemia and after 15, 30, 45, and 60 min reperfusion after 4 h cardioplegic arrest kept at 20 degrees C (control, n=10). Leukocyte-depleted reperfusion was done in the test group (n=10). The endothelium of the coronary artery was observed by scanning electron microscopy (SEM) with percent injured area of endothelial cells measured to evaluate the extent of endothelial ischemia-reperfusion injury. RESULTS: The control hearts showed 53.3, 54.3, 48.4, and 39.0% recovery of DP compared to the pre-ischemia baseline data at 15, 30, 45, and 60 min after reperfusion began respectively. Leukocyte-depleted reperfusion enhanced the recovery of DP at 45 min (81.3%, P=0.0021) and 60 min (85.8%, P=0.0005) after reperfusion compared with that in the control group. The control hearts revealed 58.8%, 59.8%, 52.6%, and 43.4% recovery of dP/dT compared to the pre-ischemia baseline data at 15, 30, 45, and 60 min after reperfusion began, respectively. Leukocyte-depleted reperfusion also enhanced the recovery of dP/dT at 45 min (93.2%, P=0.0071) and 60 min (98.8%, P=0.0011) after reperfusion compared with that in the control group. There was also improvement of the recovery of coronary flow by leukocyte-depleted reperfusion (97.2%) compared with that in the control group (58.3%) after 60 min reperfusion (P=0.0121). Scanning electron microscopy showed that 69. 7% of coronary endothelial cells were morphologically injured in the control group. In contrast, leukocyte-depleted reperfusion prevented the extent of coronary endothelial damage with less injured area (0. 5%, P=0.0002). CONCLUSIONS: Leukocyte-depleted reperfusion improved functional recovery with reduced coronary endothelial injury after long cardioplegic arrest.

Animals↗
PubMed2000

Calicheamicin-conjugated humanized anti-CD33 monoclonal antibody (gemtuzumab zogamicin, CMA-676) shows cytocidal effect on CD33-positive leukemia cell lines, but is inactive on P-glycoprotein-expressing sublines.

Calicheamicin-conjugated humanized anti-CD33 mouse monoclonal antibody, CMA-676, has recently been introduced to clinics as a promising drug to treat patients with acute myeloid leukemia (AML) in relapse. However, the mechanism of action of CMA-676 has not been well elucidated. The cytotoxic effect of CMA-676 on HL60, NOMO-1, NB4, NKM-1, K562, Daudi, and the multidrug-resistant sublines, NOMO-1/ADR and NB4/MDR, was investigated by cell cycle distribution and morphology. These studies were done by a video-microscopic system, DNA fragmentation, dye exclusion and 3H-thymidine uptake after analysis of CD33, CD34, P-glycoprotein (P-gp), multidrug resistance (MDR)-associated protein and lung-related protein on these cells. A dose-dependent, selective cytotoxic effect of CMA-676 was observed in cell lines that expressed CD33, and was dependent on the amount of CD33 and the proliferative speed of the cells. Sensitive cells were temporally arrested at the G2/M phase before undergoing morphological changes. CMA-676 is not effective on P-gp-expressing multidrug-resistant sublines compared with parental cell lines. MDR modifiers, MS209 and PSC833, restored the cytotoxic effect of CMA-676 in P-gp-expressing sublines. CMA-676 is a promising agent in the treatment of patients with AML that expresses CD33. The combined use of CMA-676 and MDR modifiers may increase the selective cytotoxic effect in multidrug-resistant AML.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

In vitro IL-12 treatment of peripheral blood mononuclear cells from patients with leukemia or myelodysplastic syndromes: increase in cytotoxicity and reduction in WT1 gene expression.

Interleukin-12 (IL-12) has potent antitumor activities. We examined whether IL-12 enhanced the cytotoxicity of peripheral blood mononuclear cells (PBMNC) and decreased leukemia cells in 30 patients with leukemia or myelodysplastic syndromes (MDS): 12 acute myeloid leukemia (AML) (five in complete remission (CR) and seven in non-CR); six chronic myeloid leukemia (CML); and 12 MDS (three refractory anemia (RA), eight RA with excess of blasts and one chronic myelomonocytic leukemia). PBMNC from patients and five healthy volunteers were cultured at 5 x 10(5)/ml parallel with or without 100 units/ml of IL-12 for 3 days. Cytotoxicity of PBMNC against K562 cells was assessed by flow cytometry. To quantify the amount of leukemia cells, WT1 mRNA was measured by competitive reverse transcription polymerase chain reaction (RT-PCR), since WT1 mRNA is considered as a marker of minimal residual disease (MRD) in leukemia or MDS. The cytotoxicity of non-IL-12-treated PBMNC of 30 patients was 13.4+/-9.3% at the effector to target (E:T) ratio of 20:1, and significantly lower than that of normal subjects (25.7+/-8.4%). The cytotoxicity increased to 30.6+/-17.9% in the IL-12-treated PBMNC. WT1 mRNA in PBMNC of five healthy volunteers was less than 10(3) copies/microg of total RNA. Following the 3-day IL-12 treatment, mean WT1 mRNA of PBMNC was reduced from 10(4.8) to 10(4.2) copies/microg of total RNA in six CML patients, from 10(5.4) to 10(4.8) copies/microg in 12 MDS patients and from 10(5.0) to 10(4.2) copies/microg in five AML patients in CR, but not reduced in five of seven AML in non-CR. These results showed that IL-12 significantly enhanced PBMNC cytotoxicity and decreased the quantity of leukemia cells in PBMNC of most patients with MDS, CML and AML in CR. IL-12 might be of considerable benefit in the elimination of MRD in patients with hematological malignancies.

Adult↗
PubMed2000

Role of P-glycoprotein in all-trans retinoic acid (ATRA) resistance in acute promyelocytic leukaemia cells: analysis of intracellular concentration of ATRA.

We analysed the relationship between all-trans retinoic acid (ATRA) resistance and P-glycoprotein (P-gp)-associated multidrug resistance (MDR) in acute promyelocytic leukaemia (APL). There was no difference in the intracellular ATRA accumulation between NB4 cells and an MDR1 cDNA-transduced NB4 subline and between ATRA-resistant NB4 cells (NB4/RA) and an MDR1 cDNA-transduced NB4/RA subline. PSC833, a MDR modifier, did not increase the intracellular accumulation of ATRA or affect the expression of CD11b, the nitroblue tetrazolium (NBT) reduction activity, the proportion of apoptotic cells or the morphology of these four ATRA-treated cell lines. Similar results were obtained in the analysis of APL cells from five patients relapsed after ATRA-induced complete remission.

ATP Binding Cassette Transporter, Subfamily B, Mem↗