Biomedical subjects

T Fujimoto

Publications and source records attributed to T Fujimoto.

At least 451 records · Page 25Linked to original sources

PubMed1990

Studies on age-dependent plasma platinum pharmacokinetics and ototoxicity of cisplatin.

The age-related difference of cisplatin (CDDP) pharmacokinetics and ototoxicity were studied in 6 children with solid tumors who received CDDP infusion. CDDP was administered intravenously for 6 hours at a dosage of 30-120 mg/m2 and plasma-free platinum concentrations were determined by atomic absorption spectrophotometry. Plasma-free platinum concentrations ranged from 1.0 to 2.1 micrograms/ml at the end of infusions and declined rapidly with T1/2 of 0.6-1.5 hours. Pharmacokinetic parameters of plasma-free platinum were analyzed in 13 CDDP infusions by the one-compartment open model method. Parameters (Ke, Cl, T1/2 and Vd) of free platinum pharmacokinetics were 0.66 hr-1, 7.71l/hr, 1.35 hr and 15.71l in the younger group (age: 1.7-6.5 years old) and 1.44 hr-1, 11.41l/hr, 0.61 hr and 8.99l in the older group (age: 12.2-15.7 years old), respectively. Up to 600 mg/m2 of the cumulative dosage of CDDP caused minimal ototoxicity in the older group; however, in the younger group, hearing loss at a high frequency zone (6000 and 8000 Hz) began to appear at a cumulative dosage of 200 mg/m2 and progressed to middle zone (3000 Hz) when dosages surpassed 400 mg/m2. These data indicate that the pharmacokinetic difference in age possesses a large distribution volume (Vd) and that slower elimination of the drug in a younger age group is an important factor for age-dependent ototoxicity.

Adolescent↗

PubMed1990

In-vitro antibacterial activity of DQ-2556 and its stability to various beta-lactamases.

DQ-2556, a new cephalosporin, showed a broad antibacterial spectrum over Gram-positive and -negative organisms. The activity of DQ-2556 against recent clinical isolates of Gram-positive cocci and Enterobacteriaceae was comparable with that of cefpirome, and superior to that of ceftazidime. DQ-2556 was almost as active as cefpirome against Pseudomonas aeruginosa, but was less active than ceftazidime. With the exception of Ps. aeruginosa, DQ-2556 was bactericidal against various organisms at either the MIC or twice the MIC. DQ-2556 bound preferentially to penicillin-binding proteins (PBPs) 2, 1 and 3 of Staphylococcus aureus, PBPs 3, 1A and 1B of Escherichia coli and PBPs 1A, 3 and 4 of Ps. aeruginosa. DQ-2556 was stable to various penicillinases and cephalosporinases, but was unstable to oxyiminocephalosporinases. The Km values of DQ-2556 for the cephalosporinases of Citrobacter freundii and Enterobacter cloacae were only two- or three-fold higher than those of ceftazidime, indicating that DQ-2556 had a relatively high affinity for these enzymes compared with other recently developed cephalosporins. The MIC of DQ-2556 for Esch. coli increased four-fold in an OmpF-deficient mutant, indicating that the OmpF porin was one of the major routes for penetration of DQ-2556 into Esch. coli cells.

Ceftazidime↗

PubMed1990

Tachyplesins isolated from hemocytes of Southeast Asian horseshoe crabs (Carcinoscorpius rotundicauda and Tachypleus gigas): identification of a new tachyplesin, tachyplesin III, and a processing intermediate of its precursor.

Tachyplesins and their analogs are antimicrobial peptides composed of 17 or 18 amino acid residues present abundantly in acid extracts of hemocyte debris of horseshoe crabs. We purified here tachyplesin isopeptides from hemocytes of two species of Southeast Asian horseshoe crabs, Carcinoscorpius rotundicauda and Tachypleus gigas, and determined their amino acid sequences. The major tachyplesin isolated from both species was identified, respectively, as tachyplesin I, which had previously been found in hemocytes of the Japanese horseshoe crab (Tachypleus tridentatus). The yield from both species was very high (more than 70 mg per 100 g wet weight of hemocytes), i.e., comparable with that from T. tridentatus. In addition to tachyplesin I, a new tachyplesin isopeptide, named tachyplesin III, was also isolated from T. gigas hemocytes, in which an arginine replaced the 15th lysine of tachyplesin I. The carboxyl-terminal residue of the isolated tachyplesins I and III was confirmed, respectively, to be an arginine alpha-amide by chemical analysis. Furthermore, a tachyplesin peptide derivative with a carboxyl-terminal extension of glycine-lysine was newly found in the hemocytes of C. rotundicauda. It appeared to be an intermediate derived from a tachyplesin precursor during processing to the mature form.

Amino Acid Sequence↗

PubMed1990

Childhood acute megakaryoblastic leukemia with internalization of hemic cells.

Two atypical cases of acute megakaryoblastic leukemia (AMKL) in infants diagnosed by immunophenotying are described. In both cases, the leukemic cells at diagnosis resembled monoblasts with reniform nuclei, fine reticular chromatin, and abundant grey-blue cytoplasm with pseudopods. In addition, these blasts frequently showed internalization of hemic cells. Therefore, the diagnosis of acute monocytic leukemia (AMOL) or malignant histiocytosis (MH) was initially suggested. However, alpha-naphthyl butyrate esterase stain was negative and immunologic studies determined megakaryocytic lineage of the blasts. Our observation in two consecutive cases of AMKL implies that there is a potential risk of misdiagnosing AMKL as AMOL or MH in infants. The incidence and significance of internalization of hemic cells by blast cells of AMKL in infancy are unknown and we cannot be certain whether these cases constitute a subgroup of AMKL in infancy.

Bone Marrow↗

PubMed1990

Distribution of fodrin in the keratinocyte in vivo and in vitro.

Distribution of fodrin in the keratinocyte, both in vivo and in vitro, was examined by immunofluorescence microscopy. In the rat epidermis in vivo, fodrin was localized in the cell periphery of the spinous layer of all the skins studied. In only the basal layer of the thick skin, however, fodrin was seen intensely in the cytoplasm. As in vitro keratinocytes, a mouse cell line (Pam 212) cultured in low (0.06 mM) as well as standard (1.87 mM) Ca2+ was examined. In low Ca2+, fodrin was observed throughout the cytoplasm without marked accumulation irrespective of the cell density. The cytoplasmic labeling in low Ca2+ looked filamentous and became aggregated when cells were treated with cytochalasin B; at least some of the aggregates coexisted with those of F-actin. In contrast, fodrin distribution was not affected with colchicine. On the other hand, in standard Ca2+, the protein became concentrated along the cell periphery and less conspicuous in the cytoplasm as the cells reached confluency. When cells were transferred from low to standard Ca2+, the distribution of fodrin changed accordingly within 180 min. The present results indicate that fodrin in the keratinocyte is likely to be associated with actin filaments and that it takes two different ways of distribution both in vivo and in vitro. The peripheral and the cytoplasmic labeling of in vivo and in vitro cells are likely to correspond. It may be that fodrin changes its localization according to the cell's proliferative activity.

Animals↗

PubMed1990

Methotrexate cytotoxicity as related to irreversible S phase arrest in mouse L1210 leukemia cells.

The association between cytotoxicity and cell cycle perturbation caused by methotrexate (MTX) was investigated in mouse L1210 leukemia cells by flow cytometric bromodeoxyuridine/DNA assay. In the range of concentrations of MTX from 10(-7) M to 10-6) M, in vitro exposure to the drug for 6 h caused a dose-dependent suppression of clonal growth of the tumor cells and S phase arrest in the cycle progression, resulting in an accumulation of cells in early S phase, in which they showed no definite increase of DNA content above G1 levels. The surviving fraction of the clonogenic cells corresponded with the fraction of cells which recovered from the S phase arrest in MTX-free medium. In mice bearing L1210 ascites tumors, a bolus injection of MTX caused the S phase arrest of the tumor cells as shown in suspension cultures, and cytokinetic recovery was observed in parallel with the regrowth of the tumor. These results showed that irreversible S phase arrest is a critical cytokinetic event associated with the cytotoxicity of MTX.

Animals↗

PubMed1990

Susceptibility of NB-I neuroblastoma cells to tumoricidal activity of monocytes activated by gamma-interferon.

The purpose of this study was to examine the susceptibility of NB-I human neuroblastoma cells to direct cellular cytotoxicity mediated by peripheral blood monocytes from pediatric cancer patients receiving chemotherapy. Nonactivated monocytes from patients showed spontaneous cytotoxicity to NB-I neuroblastoma cells (37 +/- 18%) but only marginal cytotoxicity to A375 melanoma cells (21 +/- 14%) at the effector:target cell ratio of 20:1. This spontaneous cytotoxicity to NB-I cells was observed only after greater than 24 h of cocultivation and was proportional to the effector:target cell ratio. Activation of monocytes by recombinant human interferon gamma (rIFN) (1 x 10(4) U/ml) consistently and strongly enhanced their tumoricidal activity to NB-I cells (87 +/- 6%) and this tumoricidal activity was even superior to that observed against A375 cells, which are known to be extremely sensitive to lysis by activated monocytes. In contrast, activation of monocytes by lipopolysaccharide (LPS, 1 microgram/ml) had no effect on monocyte-mediated lysis of NB-I cells, while A375 cells were equally lysed by rIFN- and LPS-activated monocytes, thus suggesting that different mechanisms are involved in the monocyte-mediated lysis of A375 melanoma and NB-I neuroblastoma cells. Susceptibility of the neuroblastoma cell line to monocyte-mediated cytotoxicity has not been reported so far and our results may have some clinical implication if this observation can be extended to other neuroblastoma cell lines as well.

Child↗

PubMed1990

Intramedullary neutrophil phagocytosis by histiocytes in autoimmune neutropenia of infancy.

We describe a case of autoimmune neutropenia of infancy in which active phagocytosis of mature myeloid cells by bone marrow histiocytes was observed. This finding in the routine hematological investigation has not been reported so far and might be helpful in suggesting the diagnosis of autoimmune neutropenia of infancy, and also in understanding the pathogenesis of peripheral neutropenia in this disease.

Autoimmune Diseases↗

PubMed1990

In vitro antibacterial activity of DR-3355, the S-(-)-isomer of ofloxacin.

DR-3355, the S-(-)-isomer of ofloxacin, possessed generally twice higher activity than ofloxacin, and its action was bactericidal. The difference in antibacterial activity of these compounds was attributable to their inhibitory activity against DNA gyrase. DR-3355 was characterized by its higher potency against gram-positive cocci and obligate anaerobes than ofloxacin and ciprofloxacin. DR-3355 was somewhat less potent than ciprofloxacin against Enterobacteriaceae and Pseudomonas aeruginosa, but was active against organisms resistant to cefteram, ceftazidime, and amikacin. The activity of DR-3355 was decreased by gyrA mutation, like that of the other quinolones, although it did not alter significantly by deficiency of outer membrane protein F or lipopolysaccharide. Moderately norfloxacin-resistant isolates of Staphylococcus aureus remained susceptible to DR-3355, but not to ciprofloxacin.

Cephalosporins↗

PubMed1990

Fodrin in the human polymorphonuclear leucocyte: redistribution induced by the chemotactic peptide.

Fodrin, a membrane skeletal protein, was found to accumulate in the posterior portion of human neutrophils polarized morphologically after stimulation by the chemotactic peptide, N-formylmethionyl-leucylphenylalanine (FMLP). In most (greater than 90%) unstimulated neutrophils, the distribution of fodrin was found to be uniform by immunofluorescence microscopy. When FMLP (10(-8)M) was applied at 25 degrees C, fodrin became polarized in about 40% of cells by 1 min, about 70% by 2 min, and about 80% by 10 min. The cells with polarized distribution decreased thereafter to about 60% of the cells at 20 min and about 20% at 60 min. Using the under-agarose system, it was confirmed that the concentration of fodrin occurred in the region opposite to the direction of chemoattraction in moving cells. By immunoelectron microscopy, most of the labeling for fodrin was observed in the filamentous cell cortex and not associated with the plasma membrane itself. In cells polarized morphologically by FMLP, the fodrin labeling became concentrated in the posterior portion of the cell; the labeling was found most densely in the granule-rich cytoplasm, while the filamentous tail region was not labeled intensely. The lamellipodium in the head region was also labeled only sparsely. The results indicate that in human neutrophils fodrin exists as a cytoskeletal protein rather than as a membrane protein and that the protein accumulates in the endoplasm of the posterior portion in migrating cells. The rearrangement is likely to modulate the organization of the actin-rich cell cortex for cell locomotion.

Carrier Proteins↗

PubMed1990

Amino acids and peptides. XXIX. Synthesis of peptide fragments related to active center of eglin c and studies on the relationship between their structure and their inhibitory activity against cathepsin G and alpha-chymotrypsin.

H-Ser-Pro-Val-Thr-Leu-Asp-Leu-Arg-Tyr-OMe, corresponding to the sequence 41-49 of eglin c, inhibited human leukocyte cathepsin G and alpha-chymotrypsin. In order to gain further insight into the relationship between the structure and the inhibitory activity against cathepsin G and alpha-chymotrypsin, peptide fragments related to the above nonapeptide were synthesized by a conventional solution method and their inhibitory activities were examined. The smallest peptide which exhibited inhibitory effects on the above enzymes was H-Pro-Val-Thr-Leu-OMe, corresponding to the sequence 42-45 of eglin c.

Amino Acid Sequence↗

PubMed1990

Characterization of slow conduction in the common type of atrial flutter--using transient entrainment.

To characterize slow conduction of the common type of atrial flutter (common AF), in which excitation wave propagated in a counterclockwise fashion, transient entrainment during the distal high lateral right atrium (HRAd) pacing and during the proximal coronary sinus (CSp) pacing was studied in 7 patients with common AF. In transient entrainment of common AF, conduction time from stimulus to CSp during HRAd pacing was always longer than that from stimulus to HRAd during CSp pacing. It was also longer than that from stimulus to CSp during HRAd pacing in 5 control patients without common AF in sinus rhythm. Return cycles at HRA and CS after cessation of rapid pacing during transient entrainment were studied. In HRAd pacing, return cycle at the proximal high lateral right atrium was almost equal to the pacing cycle length, or almost equal to or slightly shorter than the flutter cycle length (AFCL). Return cycle at CSp was almost equal to AFCL. In CSp pacing, return cycle at the distal coronary sinus was much longer than AFCL and increased at progressively shorter pacing cycle lengths. In conclusion, slow conduction was demonstrated in the lateral limb (from HRA laterally to CS) of the reentrant circuit in common AF, but it did not exhibit decremental conduction property. Return cycle at an endocardial recording site after transient entrainment in common AF does not always exhibit an uniform pattern, affected by the relative location of and the distance between the recording site, the pacing site, the reentrant circuit and the area of slow conduction.

Aged↗

PubMed1990

Signal-averaging electrocardiogram in patients with diabetes mellitus.

In order to detect silent impairment of the heart due to diabetes mellitus, the signal-averaging electrocardiograms (ECG) of 21 healthy subjects and 22 diabetic patients without ventricular tachycardia were compared. The QRS duration in the signal-averaging ECG was longer in diabetic patients than in the normal subjects (87.3 ms vs. 114.5 ms, p less than 0.01). Moreover, late potentials in the terminal portion of the QRS complex were observed in 7 diabetic patients (32%), but in only one normal subject (5%, p less than 0.01). These findings suggested that patients with diabetes mellitus frequently have intraventricular conduction disturbances, presumably due to diabetic microangiopathy.

Adult↗

PubMed1990

Cardiac sarcoidosis.

The present report describes a patient with cardiac sarcoidosis who developed complete right bundle branch block, complete atrioventricular block and subsequent congestive heart failure. The patient demonstrated no clinical evidence of systemic sarcoidosis. Upon postmortem examination, the myocardium showed extensive noncaseating granuloma with numerous multinucleated giant cells. An initial routine microscopic examination of the lung revealed no evidence of granulomatous lesions. However, an extensive microscopic examination of the lung using serial sections demonstrated inconspicuous granulomatous lesions with giant cells. Thereby, a diagnosis of sarcoidosis was made. All other organs were free of granulomatous inflammation in spite of an extensive microscopic examination through serial sections. The present case suggests that a careful and extensive microscopic examination of the other organs may be necessary to establish a diagnosis of cardiac sarcoidosis.

Cardiomyopathies↗

PubMed1990

Induction of recurrent glomerulitis with accentuated glomerular lobulation by intermittent repetition of unilateral Masugi nephritis.

In order to induce a glomerulitis with lobular features, antirabbit renal glomerular basement membrane hen serum was intravenously injected into rabbits repeatedly at intervals of 3 weeks, during the course of clamping of contralateral renal arteries for 20 min. The first injection induced disorganization of the glomerular architecture accompanied by proliferation of local fixed cells and following crowding of the proliferated cells towards the axis of the loops and peripheral recanalization which brought about a lobular appearance of glomerulus. And the repeated injections induced repetition of such processes, resulting in accentuation or exaggeration of the lobular features of the glomeruli. The glomerular lesions presented here resembled closely to those of human lobular glomerulonephritis. Accordingly, the results of this study will offer some clue to understanding of the genesis of the human glomerular disease.

Animals↗

PubMed1990

Epithelial cell clusters of distal convoluted tubules in end-stage chronic glomerulonephritis.

Differences in the pathologic changes of the proximal convoluted tubules, the cortical segments of the thick ascending limbs of the loops of Henle, and the distal convoluted tubules in the end-stage kidneys with chronic glomerulonephritis were studied by means of both light and electron microscopy. Kidneys with chronic glomerulonephritis were obtained from 8 non-dialyzed patients at autopsy and 9 dialyzed patients at the time of nephrectomy prior to renal transplantation. Epithelial cell clusters with clear cytoplasm, decreases in the luminal and outer diameters of the tubules, and thin basement membranes were observed in both the non-dialyzed and dialyzed kidneys to varying degrees. The epithelial cell clusters were more extensive and distinct in kidneys from patients with a long history of chronic glomerulonephritis and/or long-term hemodialysis. Electron microscopy of the epithelial cell clusters revealed the absence or narrowing of lumens and luminal surfaces that were smooth except for a few short microvilli. Observation of serial sections showed that these epithelial cell clusters were derived from the distal convoluted tubules belonging to obsolescent glomeruli. This form of tubular change is quite different from the well-known atrophy of the proximal convoluted tubules belonging to obsolescent glomeruli in chronic glomerulonephritis.

Adult↗

PubMed1990

Bilaterally persistent sciatic arteries.

A very rare developmental anomaly showing bilaterally persistent sciatic arteries was found in a cadaver of 89 year old female. Both right and left sciatic arteries arose from the internal iliac arteries and appeared between the piriformis and superior gemellus muscles at the buttock, being about 10 mm in diameter. Each artery, which accompanied by the companion vein, i.e. sciatic vein, sent the branches to the gluteus maximus and the flexor muscles of thigh. On the other hand, the femoral arteries of both lower limbs were smaller than usual, measuring 4.7 mm in left and 5.2 mm in right. The terminal vessels of those were joined to the sciatic arteries at the popliteal fossa. In addition, the present case also had another developmental anomaly, i.e. superficial brachial artery in the right upper limb.

Aged↗

PubMed1990

Gut formation after transection of the midgut loop in the chick embryo.

The primitive gut in vertebrates can be divided into the foregut, midgut, and hindgut. The midgut forms the midgut loop or the intestinal loop, which rotates as it develops the small and large intestines. We examined the effects of transection of the midgut loop on the subsequent development of the intestine in chick embryos by their out-of-the-shell incubation. The development of the embryo and the intestines out of the shell was nearly identical to that usual in-the-shell incubation. The rotation of the midgut loop began in stage 27 (5 days of incubation) and was completed in stage 36 (10 days of incubation) after counterclockwise rotation through 180 degrees. In experimental groups, the midgut loop was transected immediately before or in the early stages of rotation (stages 27-33) proximally or distally to the apex of the loop. Transecting of the midgut loop caused little effects on its subsequent rotation regardless of the time or the site of transection although the secondary loop formation of intestine was poor in some cases. The stumps of the transected intestine were repaired and closed. After closure of the stumps, the proximal segment of the intestine was dilated in some cases. The secondary loop formation, or convolution of the intestine didn't occur in some dilated cases.

Animals↗