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Biomedical subjects

T Fujimoto

Publications and source records attributed to T Fujimoto.

At least 289 records · Page 16Linked to original sources
PubMed1995

Large equine blastocysts are damaged by vitrification procedures.

Viability following vitrification of equine blastocysts with different sizes was investigated in vitro. Twenty-four blastocysts were classified into three groups according to their diameters (< 200 microns, 200-300 microns and > 300 microns; n = 8 each). The solution used for vitrification was defined as EFS and contained 40% ethylene glycol, 18% Ficoll and 0.3 M sucrose in modified-phosphate-buffered saline (m-PBS). During pretreatment with 20% ethylene glycol in m-PBS for 20 min, the larger blastocysts responded to the osmotic pressure caused by 20% ethylene glycol more slowly than the smaller blastocysts. Single blastocysts were loaded into the EFS in 0.25-mL straws, left to stand for 1 min and vitrified in nitrogen vapour. After thawing for 20 s in water (20 degrees C), a fractured zona pellucida or capsule was seen in: 1 of 8 blastocysts < 200 microns in diameter; 1 of 8 blastocysts 200-300 microns in diameter; and 2 of 8 blastocysts > 300 microns in diameter. When the blastocysts were cultured for 48 h in TCM199 supplemented with 10% fetal bovine serum at 37 degrees C in 5% CO2 in air, 7 of 8 (88%) blastocysts < 200 microns in diameter and 6 of 8 (75%) blastocysts 200-300 microns in diameter developed with re-expansion of the blastocoele. However, the developmental ability of blastocysts > 300 microns in diameter (2 of 8, 25%) was significantly lower than that of blastocysts < 200 microns in diameter (P < 0.05).

Animals↗
PubMed1995

Pharmacokinetics of all-trans retinoic acid in pediatric patients with leukemia.

Since all-trans retinoic acid (ATRA) induces complete remission in a high proportion of patients with acute promyelocytic leukemia (APL), and its effectiveness appears to be related to the plasma or serum level, a pharmacokinetic study of ATRA was undertaken in nine patients with various leukemias. After oral administration at a dose of 30 mg/m2, the time required to reach the peak plasma level of ATRA (20-1198 ng/ml) was between 120 and 240 min and the apparent plasma elimination half life was 21-51 min. In addition, 13-cis retinoic acid was detected in the plasma of seven patients, indicating the occurrence of ATRA isomerization in vivo. ATRA therapy did not induce complete remission in all patients, even when high plasma levels were achieved. Among the six APL patients given ATRA therapy, one who failed to respond had a very low plasma ATRA level. These findings suggest that it may be useful to monitor plasma levels during oral ATRA therapy in order to achieve an appropriate treatment regimen.

Adolescent↗
PubMed1995

Inositol 1,4,5-trisphosphate receptor-like protein in plasmalemmal caveolae is linked to actin filaments.

We reported that a plasmalemmal inositol 1,4,5-trisphosphate receptor-like protein (PM InsP3R-L) is localized in caveolae of various non-neuronal cells in vivo (Fujimoto et al. (1992) J. Cell Biol. 119, 1507-1513). In the present study, we investigated the distribution of PM InsP3R-L in cultured cells. In mouse epidermal keratinocytes (Pam 212) cultured in standard Ca2+ (1.8 mM), PM InsP3R-L was distributed densely in the vicinity of cell-to-cell contacts. In contrast, when Pam cells were cultured in low Ca2+ (0.06 mM) without making cell-to-cell contacts, PM InsP3R-L was observed randomly; by restoring the Ca2+ concentration, the circumferential actin filaments became obvious and the density of PM InsP3R-L increased in the contact region. Treatment of Pam cells with cytochalasin D caused aggregation of caveolae where PM InsP3R-L as well as F-actin and fodrin were localized. In bovine aortic endothelial cells, PM InsP3R-L was aligned along actin filaments crossing the cytoplasm in various directions. PM InsP3R-L of Pam cells was hardly extracted by treatment with 0.5% Triton X-100 or 60 mM octyl-glucoside in a cytoskeleton-stabilizing buffer for 15 minutes at 4 degrees C. The results show that the distribution of caveolae bearing PM InsP3R-L changes when the actin cytoskeleton is modified. They also indicate that the association of PM InsP3R-L with actin filaments may mediate the redistribution of caveolae. Since caveolae are thought to be related to signal transduction, their location defined by the actin cytoskeleton may affect the site where cellular reaction is to occur in response to various stimuli.

Actins↗
PubMed1995

Functional magnetic resonance imaging of the human motor cortex.

Functional magnetic resonance (MR) imaging of the brain was performed during motor task activation in five normal subjects and a patient with meningioma using conventional fast low-angle shot sequences and a 2.0 T system. A high intensity area in the motor cortex was observed in all normal subjects. Single-slice studies showed the right-sided finger task produced an increase of 1.9-23.5% (6.67 +/- 4.36%) in the signal intensity of the left motor cortex, while the left-sided finger task increased the signal by 1.5-18.2% (6.09 +/- 3.34%) in the right motor cortex. There was no significant difference between the sides. Multiple-slice studies also showed the activated motor cortex as a high intensity area. The maximum signal intensity increase in the activated motor area was 11.0% for the left motor cortex and 8.8% for the right motor cortex. There was no significant difference between the sides. Preoperative mapping of the patient with meningioma showed that the motor cortex was displaced posteriorly by the tumor. Functional MR imaging is possible with a standard MR imaging system and conventional gradient echo sequences. Useful clinical information can be obtained by preoperative mapping of the motor cortex.

Afferent Pathways↗
PubMed1995

4-oxo retinoic acid for refractory acute promyelocytic leukemia in children with all-trans retinoic acid therapy.

Therapy with all-trans retinoic acid (ATRA) achieves complete remission in a high proportion of patients with acute promyelocytic leukemia (APL), but the efficacy is reported to relate to plasma ATRA level after oral administration. The pharmacokinetics of ATRA and 4-oxo all-trans retinoic acid (4-oxo ATRA), a metabolite of ATRA, were studied in four children with APL at the time of initial oral administration. After administration of ATRA at a dose of 30 mg/m2, the peak plasma ATRA level was 20-741 ng/ml and was reached at 60-120 min. The patient with the lowest peak plasma level did not achieve complete remission and had a very high 4-oxo ATRA level compared to the patients with complete remission. These findings suggest that accelerated metabolism of ATRA plays a role in the failure of this agent in the patients without remission.

Administration, Oral↗
PubMed1995

[A case of nephrotic syndrome associated with severe interstitial pneumonitis due to cyclophosphamide whose life was saved by steroid pulse therapy].

A 53-year-old man was admitted for treatment of nephrotic syndrome due to membranous nephropathy. Since he did not improve with prednisolone alone, cyclophosphamide was administered concomitantly. However, this induced severe interstitial pneumonitis, which was not cured by discontinuation of the drug, but disappeared completely with six episodes of methylprednisolone pulse therapy. The incidence of cyclophosphamide-induced interstitial pneumonitis is low, but the mortality is high. Since cyclophosphamide is often used for the treatment of nephrotic syndrome, attention should be focused on the incidence of interstitial pneumonitis. Discontinuation of cyclophosphamide and intensive therapy are required when it occurs.

Anti-Inflammatory Agents↗
PubMed1995

Cell cycle kinetics in childhood acute leukemia studied with in vitro bromodeoxyuridine labeling, Ki67-reactivity, and flow cytometry.

Cell cycle kinetics of childhood acute leukemia were determined by the in vitro labeling of marrow blast cells with bromodeoxyuridine (BrdUrd) and subsequent flow cytometry of BrdUrd/DNA and Ki67/DNA in 18 patients with acute lymphocytic leukemia (ALL) and eight patients with acute nonlymphocytic leukemia (ANLL). The BrdUrd-labeling index (BrdUrd-LI) and the duration of S phase (Ts) were calculated from the slope of the regression line obtained by plotting the serial labeling indices against the labeling time. The Ts and potential doubling time (DTpot) of marrow leukemia cells varied from 6.1 to 34.3 h (median 14.3 h) and 1.1 to 20.7 days (median, 7.3 days), respectively. The duration of the total cell cycle time (Tc) which was determined by the Ki-67-derived growth fraction (Ki-67-GF) varied from 14.0 to 112.5 h (median 43.2 h). BrdUrd-LI, DTpot, Ki-67-GF and Tc were significantly correlated with the subtypes (early B-ALL, T/B- ALL and ANLL) of the disease. The median values of LI and GF were much lower in ANLL than in ALL. However, the low proliferative activity of ANLL was not accompanied by a prolonged duration of the total cell cycle time. The longest median duration of Tc was noted in early B-ALL (75.2 h) and the median Tc in ANLL (36.7 h) was close to that in T/B-ALL (34 h). Ts appeared to be rather independent of subtypes of the disease. These results show that there are distinct in vitro growth characteristics in relation to the subtypes of childhood acute leukemia.

Bone Marrow↗
PubMed1995

[Expression of a proliferation associated-nuclear antigen defined by Ki-67 monoclonal antibody in childhood acute leukemia].

The growth fraction of childhood acute leukemia was evaluated by the immunostaining with the monoclonal antibody "Ki-67", which reacts with a nuclear antigen in proliferating cells. Ki-67 labeling rates (the percentage of Ki-67 positive cells in the total cells analyzed) greatly varied from patient to patient (0.0% approximately 49.2%). The mean value of the Ki-67 labeling rates was significantly higher in ALL than in ANLL (23.6% vs 5.6%, p < 0.001). In ALL, the Ki-67 labeling rates correlated with the proportion of S-phase cells determined by DNA flow cytometry (FCM) (r = 0.82) High Ki-67 labeling rates were preferably seen in ALL with favorable prognostic factors, although the correlation was not statistically significant. These results suggest that Ki-67 labeling rates reflect the differences in proliferative activity of bone marrow blast cells in childhood acute leukemia and is useful to determine the treatment schedule of cycle specific drugs.

Adolescent↗
PubMed1995

[Detection of loss of heterozygosity by microsatellite probe and DNA content analysis].

We examined replication error (RER) and loss of heterozygosity (LOH) in the region of microsatellites in 60 cases of resected lung cancer. We used microsatellite probes for the short arm of the 2nd chromosome (D2S123, D2S136), the short arm of the 3rd chromosome (D3S1067), and the short arm of the 17th chromosome (TP53). According to stage, the frequency of LOH was 25% in stage I, 33% in stage II, 44% in stage IIIA, 11% in stage III B, and 63% in stage IV. According to histological classification, the frequency of LOH was 41% for squamous cell carcinoma, 24% for adenocarcinoma, and 100% for small cell carcinoma. According to microsatellite probe results, the frequency of LOH was 6.7% for D2S123, 5.0% for D2S136, 16.7% for D3S1067, and 18.3% for TP53. Two of the 60 cases showed RER. One case was stage I squamous cell carcinoma, and the other was stage IV adenocarcinoma. Except for stage III B,LOH in the microsatellite region increases with the stage. LOH is often detected in the order of small cell carcinoma, squamous cell carcinoma, and adenocarcinoma. According to the chromosome number, LOH is detected more often in the 3rd and 17th chromosomes than in the 2nd chromosome. In 20 cases with LOH, only two showed DNA diploidy. Compared to LOH of the microsatellite region, DNA content analysis by flow cytometry has accuracy problems.

Aneuploidy↗
PubMed1995

[Current status in treatment of childhood cancer].

The principles of cancer chemotherapy applied to adult patients today have been substantially derived from experience of cancer in children. Studies of pediatric solid tumors also provided the first evidence that chemotherapy combined with surgery and/or radiotherapy could markedly enhance the curative potential of these local modalities. Conceptual advances in cancer chemotherapy revealed the superiority of intermittent chemotherapy over continuous low-dose therapy with respect to tumor cell kill and the recovery of normal cells. Childrens' Cancer and Leukemia Study Group of Japan applied intensive intermittent chemotherapy for maintenance therapy for leukemia, malignant lymphoma and to adjuvant chemotherapy for solid tumors. Event-free survival rate in treatment of childhood cancer by the Department of Pediatrics, Aichi Medical University, has markedly improved: ALL, 70%; malignant lymphoma, 50%; ANLL, 33%; hepato-blastoma, 100%; osteosarcoma, 65%; neuroblastoma, 54%; and rhabdomyosarcoma, 51%. The 14% rate for brain tumors was the only exception. Current Phase I and II trials based on pharmacokinetics and pharmacodynamics in children were reviewed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Focal fatty masses of the pancreas.

Five patients with solitary fatty mass of the pancreas examined with CT and ultrasound (US) were evaluated. The areas of fat replacement were located in the pancreatic neck, body or tail. The size ranged from 4 to 30 mm in the longest diameter. The shape varied from roundish, to ovoid to semicircular, and the contour was universally well defined. The internal structure was homogeneous in 3 patients, but in one case there were thin septa and, in another, a slightly hyperdense part in the peripheral portion. All the masses except the smallest one were in part contact with pancreatic fat. CT showed fat with the same density as the peripancreatic fat and low HU units. The mass was hypoechoic in 2 cases and hyperechoic in one. The masses in the tail of the pancreas were not detected by US.

Adipose Tissue↗
PubMed1995

p53 gene mutation and loss of heterozygosity are associated with increased risk of disease progression in adult T cell leukemia.

Although the prototype of adult T cell leukemia (ATL) is an aggressive T cell neoplasm, ATL manifests four major clinical subtypes, acute, lymphoma, chronic, and smoldering. We studied the relationship between p53 gene alteration and clinical features in 34 patients with ATL, 14 acute type, 15 chronic type, and five crisis type transformed from chronic type. Using a polymerase chain reaction/single strand conformation polymorphism (PCR/SSCP) assay, followed by nucleotide sequencing, we detected mutations of the p53 gene in six of the 14 acute type patients, two of the five crisis type, and one of the 15 chronic type patients. Gene dosage studies, using PCR amplification and Southern blotting, showed loss of heterozygosity (LOH) of the p53 gene in four of the 14 acute type patients, two of the five crisis type, and one of 14 chronic type patients examined. These observations indicated that the frequency of p53 gene alterations in the acute and crisis types of ATL was markedly higher than that in chronic type, suggesting that p53 gene alteration plays a role in the disease progression of ATL.

Adult↗