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Biomedical subjects

F Ito

Publications and source records attributed to F Ito.

At least 199 records · Page 11Linked to original sources
PubMed1987

Phase II study of oral VP-16-213 in small cell lung cancer.

The soft, gelatin capsule of VP-16-213 (etoposide) was given orally and evaluated in a Phase II study of 56 patients with histologically confirmed small cell lung cancer. The drug was given in a dose of 200 mg/body/day orally for 5 consecutive days, and the courses were repeated every 3 to 4 weeks depending upon the individual patient recovery from myelosuppression. An overall objective response was obtained in 17 patients (30%), five previously treated (23%) and 12 untreated (35%). The median days for response after the start of treatment was 14 d (range, 5 to 64), and the median duration of response was 62 days (range, 28 to 278). The dose-limiting factor was leukopenia, while thrombocytopenia was also experienced. Gastrointestinal reactions to toxicity and alopecia were also observed, but they were not overwhelming. The study demonstrated that the VP-16-213 soft gelatin capsule given orally is effective against small cell lung cancer without clinical cross-resistance to other cytotoxic agents. Its usefulness in combination chemotherapy is thus suggested.

Administration, Oral↗
PubMed1987

Low pH induced membrane fusion of lipid vesicles containing proton-sensitive polymer.

For the purpose of cytoplasmic delivery of aqueous content in liposomes through endosomes, we synthesized a pH-sensitive polymer, cetylacetyl(imidazol-4-ylmethyl)polyethylenimine (CAIPEI), which generates polycations at acidic pH. CAIPEI in its aqueous phase caused aggregation of sonicated vesicles composed of phosphatidylserine (PS) and phosphatidylcholine (PC) (molar ratio 1:4) when the pH of the solution was lowered. The polymer also induced membrane intermixing as measured by resonance energy transfer between vesicles containing N-(7-nitro-2,1,3-benz[d]oxadiazol-4-yl)phosphatidylethanolamine and those containing N-Rhodamine phosphatidylethanolamine at pH 4-5, while the addition of CAIPEI caused neither aggregation of PC vesicles nor the intermixing of liposomal membranes between PC and PC/PS vesicles at any pH. The CAIPEI-induced membrane intermixing was dependent on the polymer/vesicle ratio rather than on the polymer concentration. Then the polymer was incorporated into the bilayers of PC vesicles. These CAIPEI vesicles also caused membrane intermixing with liposomes containing PS under acidic conditions. The reconstituted CAIPEI did not reduce the trapping efficiency of vesicles or increase their permeability to glucose even at low pH. The vesicles caused the low pH induced aggregation and membrane intermixing with other negatively charged liposomes containing phosphatidic acid or phosphatidylglycerol. These results suggest that the protonation of the polymer at acidic pH endows the CAIPEI vesicles with the activity to fuse with negatively charged liposomes.

Hemolysis↗
PubMed1987

Possible fusimotor innervation to frog muscle spindles.

In some muscle spindles located in or near the red area of semitendinosus muscle of the bull frog, a fine motor axon innervates the intracapsular compact zone, without any branches onto the extrafusal muscle fibers. The fine motor axon is 3.9 microns in mean diameter (measured in living axon) and 9.8 m X s-1 in mean conduction velocity at 20 degrees C. A ramp-and-hold stretch during 20 Hz repetitive stimulation of the fine motor axon markedly increased the rate of afferent discharges during static phase. Histochemical studies indicated depletion of glycogen in a compact zone along a small diameter intrafusal muscle fiber of the muscle spindles frozen immediately after tetanic stimulation of the fine motor axon. These results suggest that the fine motor axon is a fusimotor system in the frog muscle spindle.

Action Potentials↗
PubMed1987

Intramembrane particles and terminal responses following denervation of frog muscle spindles.

The sizes and population density of intramembrane particles in the non-myelinated sensory nerve terminals of frog muscle spindles were studied in comparison with changes in the responses to spindles to stretch 1-28 days after denervation. The sciatic nerve in the right leg was cut at the dorsal part of the hip joint. Spindle receptors in the left leg were used as controls. Muscle spindles were isolated from semitendinosus and iliofibularis muscles. The mean density of particles, which occurred mainly on the protoplasmic (P) face, declined rapidly to 60% of the control values 2 days after denervation, 30% after 4 days and to less than 10% after 7 days. The mean diameter of particles changed from 8.0 +/- 1.5 nm in the control to 12.8 +/- 2.5 nm 7 days after denervation. No significant difference between the results for the trunks (greater than 2 micron in diameter) and the branches (less than 0.5 micron) of the non-myelinated axons was observed. The peak rate of afferent discharges during a ramp-and-hold stretch survived up to 4 days after denervation, whereas the static component disappeared after 3 days. It is suggested that the decline to less than 20% of the control density of particles removes the mechanosensitivity of the sensory endings.

Animals↗
PubMed1987

Tumor necrosis factor-induced permeability increase of negatively charged phospholipid vesicles.

The effect of human tumor necrosis factor (TNF) on the permeability properties of liposomes containing phosphatidylserine at pH 5-6, as demonstrated by the calcein efflux. However, it did not induce any permeability change in such liposomes at neutral pH. The TNF-induced calcein efflux was also observed when an other acidic lipid was used as a component of the liposomes, i.e., phosphatidic acid or dicetyl phosphate. On the other hand, liposomes composed of neutral phospholipids such as phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin showed little increases in permeability when incubated with TNF above pH 5.0. The TNF-induced permeability change was inhibited by the addition of polyaspartic acid, while it was not affected by the presence of 0.5 mM calcium ions. These data suggest that the negative charges on the liposomal surface trigger the interaction between TNF and liposomes. However, when the pH of the reaction mixture was decreased to 4.5, TNF-induced calcein efflux was observed even from neutral liposomes. When TNF was incubated with 8-anilinonaphthalene-1-sulfonic acid, the fluorescence intensity of this fluorophore increased with a decrease in the pH of the solution from 7 to 5, and a drastic increase in fluorescence was observed at pH 4.5. These data suggest that the hydrophobic region of TNF is also important for liposomal damage. Furthermore, the potencies of TNF and its derivative as to the induction of the permeability change paralleled their cytotoxic effects on mouse L929 cells, suggesting that the effect of TNF on liposomal membranes is related to its biological action.

Anilino Naphthalenesulfonates↗
PubMed1987

Distinct effects of Na+ and Li+ on the induction of morphological changes in A431 cells mediated by epidermal growth factor.

Epidermal growth factor (EGF) induced the formation of thin sheetlike extensions (lamellipodia) and filamentous extensions at the edges of colonies of A431 cells. To determine the necessary processes for the induction of the morphological changes mediated by EGF, the effects of a variety of ions on these changes were examined. In a NaCl solution supplemented with CaCl2, MgCl2 and glucose, no EGF-induced morphological changes were observed. However, when the NaCl was replaced with LiCl, fingerlike extensions were formed, but sheetlike extensions were not. Addition of vanadate to the NaCl solution also induced fingerlike extensions in cells treated with EGF. In contrast, sheetlike lamellipodia were formed in EGF-treated cells by the addition of K+ or PO4(3-) to the NaCl solution or by the addition of PO4(3-) to the LiCl solution. These findings indicate that Li+, K+, PO4(3-) and vanadate are involved in the processes of EGF-induced morphological changes. Since vanadate and Li+ have been shown to inhibit phosphatases, an EGF-dependent phosphorylation step may play an important role in the induction of the morphological changes observed.

Carcinoma, Squamous Cell↗
PubMed1987

A case of interstitial 1q deletion [46,XY,del(q25q32.1)].

A 10-year-old male with interstitial deletion of chromosome 1[46,XY,del(1)(q25q32.1)] is reported. Clinical features of the patient included dwarfism, severe mental retardation, microcephaly, flat nasal bridge, low-set ears, short neck, brachydactyly, clinodactyly of the 5th fingers and bilateral cryptorchidism. Comparison of phenotypic characteristics of the present case with those of six cases previously described with similar deletions of chromosome 1 permits the delineation of an identifiable syndrome.

Abnormalities, Multiple↗
PubMed1987

Nonsurgical management of ureteral fistulas.

The combined procedure by antegrade introduction of the guidewire and retrograde placement of ureteral stents was successfully performed for the conservative management of postoperative ureteral fistulas in two patients. Superselector guidewire and ureteral bougie catheter are of use to facilitate difficult stent placement for severe narrowing accompanied with the dehiscent ureter.

Adult↗
PubMed1986

The fusogenic effect of synthetic polycations on negatively charged lipid bilayers.

The effect of synthetic polycations, polyallylamine, and polyethylenimine, on liposomes containing phosphatidylserine was investigated along with that of polylysine and divalent cations. The addition of polycations caused aggregation of sonicated vesicles composed of phosphatidylserine and phosphatidylcholine (molar ratio 1:4) as determined by measuring the turbidity changes. Liposomal turbidity increased 10 times compared with that of control liposomes at charge ratios of polymer/vesicle from 0.23 (polylysine) to 2.5 (linear polyethylenimine), while the turbidity was unchanged by the addition of Ca2+ or Mg2+ at charge ratios up to 500. These polycations also induced intermixing of liposomal membranes as indicated by resonance energy transfer between fluorescent lipids incorporated in lipid bilayers, without inducing drastic permeability changes as determined from the calcein release. Fifty percent intermixing of liposomes (0.05 mM as lipid concentration) was induced by these polycations at charge ratios of around 1.0. However, the highest resonance energy transfer was produced by the addition of polyallylamine, which caused multicycles of membrane intermixing between vesicles. Polycation-induced membrane intermixing and permeability changes of phosphatidylserine liposomes were also investigated. At charge ratios of around 1.0, these polymers caused resonance energy transfer of fluorescent lipids incorporated in separate vesicles; however, polyallylamine and branched polyethylenimine also caused permeability increases of liposomal membranes. Membrane intermixing and permeability changes of phosphatidylserine vesicles induced by polyallylamine were dependent on the polymer/vesicle charge ratio, and were different from those induced by Ca2+ since the latter caused half-maximal membrane intermixing or permeability change of phosphatidylserine vesicles at about 1 mM at the liposomal concentrations investigated.

Cations↗
PubMed1986

4-Methylumbelliferyl lipase in human and mouse brain: a possible localization in myelin.

4-Methylumbelliferyl (4-MU) lipase activity in human and mouse brain, measured with 4-MU palmitate, was characterized with respect to effects of pH and detergents, and subcellular and myelin localization. Purified myelin isolated by Norton's procedure [J. Neurochem. 21, 749-757 (1983)] contained higher specific activity of 4-MU lipase, particularly in alkaline pH. Myelin lipase activity was markedly affected by the addition of different types of detergents, the amount of detergents added, and substrate. The optimal pH in myelin was bimodal--pH 4.5 and up to 8.0, respectively. These data indicate that myelin possesses 4-MU lipase activity at alkaline pH, with lower levels at acidic pH.

Animals↗