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K Fujimoto

Publications and source records attributed to K Fujimoto.

At least 703 records · Page 39Linked to original sources
PubMed1989

Combination effect of recombinant human interleukin-1 alpha with antimicrobial agents.

Combination effects of recombinant human interleukin-1 alpha with ceftazidime, moxalactam, gentamicin, enoxacin, amphotericin B, miconazole, or an immunoglobulin preparation were evaluated in systemic infections with Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans in normal mice and systemic infection with P. aeruginosa in mice with leukopenia induced by preadministration of cyclophosphamide. Synergistic effects were generally observed at interleukin-1 alpha doses as low as 1 to 30 ng per mouse with most combinations. The results show the possibility that recombinant human interleukin-1 alpha could be of help for treating obstinate infections not successfully treated with antimicrobial agents alone.

Animals↗
PubMed1989

Stereospecific feeding modulation by endogenous organic acid gamma-lactone in rats.

Stereospecificity of 3,4-dihydroxybutanoic acid gamma-lactone (3,4-DB) and 2,4,5-trihydroxypentanoic acid gamma-lactone (2,4,5-TP) in their effects on feeding behavior and humoral factors was assessed by infusion into the rat third cerebroventricle. Initial transient food intake was most potently affected by infusion of 2.50 mumol of the 2S,4S-stereoisomer of 2,4,5-TP (80%) at 1100 h. Among the others, 2.50 mumol of the 2R,4S-isomer was somewhat potent in feeding elicitation (20%). Feeding induced by these isomers was not accompanied by periprandial drinking. Ambulation increased with elicitation of feeding. During the first dark period after infusion at 1940 h, 2.50 mumol of the 3S-isomer of 3,4-DB decreased food intake, including reduced meal size, and prolonged postprandial intermeal interval, but the 3R-isomer did not. Potent hypoglycemia with hyperinsulinemia was caused by the 2S,4S-isomer of 2,4,5-TP, and the S-isomer of 3,4-DB caused responses that were reciprocal to those to 2,4,5-TP. The remaining isomers did not affect feeding or humoral factors. The results suggest that the S- or S,S-stereo-isomer of the endogenous organic acid gamma-lactones may be important in modulating food intake through the hypothalamus.

4-Butyrolactone↗
PubMed1989

Neuronal histamine modulates feeding behavior through H1-receptor in rat hypothalamus.

To clarify the physiological role of hypothalamic neuronal histamine in control of food intake, ingestive behavior and neuronal activity were investigated under blockade or diurnal fluctuation of hypothalamic neuronal histamine. Histamine H1- but not H2-receptor antagonist potently induced feeding in a dose-related manner after infusion into rat third cerebroventricle at 1100 h. Elicitation was attenuated after infusion at 1940 h when histamine content in the hypothalamus was low and was abolished after intraperitoneal pretreatment with 0.11 mmol alpha-fluoromethylhistidine (alpha-FMH), a specific suicide inhibitor of histidine decarboxylase. Electrophoretic application of a histamine H1-receptor antagonist to ventromedial hypothalamic neurons specifically suppressed activities of glucose-responding neurons that are related to food intake. The suppressive effect was also attenuated by intraperitoneal pretreatment with alpha-FMH. These results suggest that feeding induced by histamine H1-receptor antagonists is due to blockade of neuronal histamine at the site of histamine H1-receptors, at least in part, in the ventromedial hypothalamus and that diurnal fluctuation of feeding behavior may reflect circadian variation of neuronal histamine level.

Animals↗
PubMed1989

Blunted hypoxic ventilatory drive in subjects susceptible to high-altitude pulmonary edema.

It has been proposed that subjects susceptible to high-altitude pulmonary edema (HAPE) show exaggerated hypoxemia with relative hypoventilation during the early period of high-altitude exposure. Some previous studies suggest the relationship between the blunted hypoxic ventilatory response (HVR) and HAPE. To examine whether all the HAPE-susceptible subjects consistently show blunted HVR at low altitude, we evaluated the conventional pulmonary function test, hypoxic ventilatory response (HVR), and hypercapnic ventilatory response (HCVR) in ten lowlanders who had a previous history of HAPE and compared these results with those of eight control lowlanders who had no history of HAPE. HVR was measured by the progressive isocapnic hypoxic method and was evaluated by the slope relating minute ventilation to arterial O2 saturation (delta VE/delta SaO2). HCVR was measured by the rebreathing method of Read. All measurements were done at Matsumoto, Japan (610 m). All the HAPE-susceptible subjects showed normal values in the pulmonary function test. In HCVR, HAPE-susceptible subjects showed relatively lower S value, but there was no significant difference between the two groups (1.74 +/- 1.16 vs. 2.19 +/- 0.4, P = NS). On the other hand, HAPE-susceptible subjects showed significantly lower HVR than control subjects (-0.42 +/- 0.23 vs. -0.87 +/- 0.29, P less than 0.01). These results suggest that HAPE-susceptible subjects more frequently show low HVR at low altitude. However, values for HVR were within the normal range in 2 of 10 HAPE-susceptible subjects. It would seem therefore that low HVR alone need not be a critical factor for HAPE. This could be one of several contributing factors.

Adult↗
PubMed1989

Endothelium-dependent relaxation of human basilar arteries.

We studied the effects of acetylcholine and calcium ionophore A23187 on human basilar artery rings. Among 11 arteries, both agents produced significant relaxations in five, A23187 but not acetylcholine caused a response in six, and neither agent was effective in four. After rubbing off the endothelium, the relaxations induced by both agents were significantly attenuated. Indomethacin (a cyclooxygenase inhibitor) and AA861 (a specific inhibitor of 5-lipoxygenase) did not but SKF525A (an inhibitor of cytochrome P450-dependent monooxygenase) did significantly inhibit the acetylcholine-induced relaxation in human basilar arteries. On the other hand, AA861 inhibited while neither indomethacin nor SKF525A had any effect on the A23187-induced relaxation. Our results suggest that different mechanisms may be involved in acetylcholine and A23187-induced relaxations in human basilar arteries.

Acetylcholine↗
PubMed1989

Ultracytochemistry of calmodulin binding sites in myocardial cells by staining of frozen thin sections with colloidal gold-labeled calmodulin.

Calmodulin (CaM) has been implicated as a multifunctional regulator of Ca2+ in the cytoplasm of cells. We have recently introduced biologically active colloidal gold-labeled CaM as a marker for identifying potential CaM binding sites (unoccupied by endogenous CaM at the time of fixation) by electron microscopy and have stained frozen thin sections of rat cardiac muscle with this conjugate. In the presence of Ca2+, gold particles indicating CaM binding sites were found localized on the sarcoplasmic reticulum, mitochondria, and gap junctions. Control tissue sections treated with EGTA or exposed to excess amounts of unlabeled native CaM before staining showed no binding. We believe that cytochemistry of potential CaM binding sites revealed by staining with labeled exogenous CaM is useful in correlating known biochemical reactions of CaM with particular cell activities.

Animals↗
PubMed1989

Studies on orally active cephalosporin esters. II. Chemical stability of pivaloyloxymethyl esters in phosphate buffer solution.

The degradation kinetics of pivaloyloxymethyl (POM) esters of cephalosporins in phosphate buffer solution (pH 6-8) were investigated. The degradation of the starting delta 3 cephalosporin ester proceeded mainly via isomerization to the delta 2 ester and subsequent hydrolysis to the delta 2 acid. Hydrolysis to the delta 3 acid (the parent acid) was very slow. Analysis of the rate constants indicated that the isomerization rate k12 was approximately equal to the apparent degradation rate of the delta 3 ester kdeg, and slower than the hydrolysis rate of the delta 2 ester k24. The isomerization process to the delta 2 ester was found to be the rate-determining step in the degradation of cephalosporin esters. The substituent at the C-3 position of the cephalosporins affected the degradation kinetics. The degradation was accelerated by increase of pH, buffer concentration and added protein.

Administration, Oral↗
PubMed1989

Studies on orally active cephalosporin esters. III. Effect of the 3-substituent on the chemical stability of pivaloyloxymethyl esters in phosphate buffer solution.

The effect of substituents at the C-3 position on the degradation kinetics of the pivaloyloxymethyl (POM) ester of delta 3 cephalosporin in phosphate buffer solution (pH 6-8) was investigated. In the degradation, the isomerization process to the delta 2 ester was the rate-determining step. In this study, the logarithm of the isomerization rate to the delta 2 ester (log k12) correlated with the carbon-13 nuclear magnetic resonance chemical shift difference value at C-3 and C-4 of the delta 3 ester (delta delta (4-3)). The energy level of the lowest unoccupied molecular orbital (LUMO) of the delta 3 esters also correlated with log k12. The electronic properties at the C-2 position had no effect on the isomerization reaction. On the other hand, the logarithm of the isomerization rate back to the delta 3 ester (log k21) correlated with the van der Waals volume (MV) of the 3-substituent. These results show that the substituent at the C-3 position influences mainly the electronic structure of the conjugated pi-bond system (C3 = C4 - C4 = O) and consequently affects the feasibility of isomerization to the delta 2 ester, i.e., the stability to degradation.

Administration, Oral↗
PubMed1989

Studies on orally active cephalosporin esters. IV. Effect of the C-3 substituent of cephalosporin on the gastrointestinal absorption in mice.

The effect of the C-3 substituent on the oral absorbability of pivaloyloxymethyl (POM) ester of cephalosporin in mice is described. The C-3 substituent affects the physicochemical and biochemical properties of POM ester, such as lipophilicity, water solubility, chemical stability and enzymatic stability. Quantitative analyses of the relationships between these properties and the oral bioavailability have been attempted. Lipophilicity made a parabolic contribution to the absorption. The optimum log P octanol/water value was estimated to be around 2.22. The chemical isomerization of the cephem double bond from delta 3 to delta 2 in the intestinal lumen prior to absorption contributed linearly to decrease of absorption. In the case of POM ester having a larger isomerization rate, more delta 2 isomer was detected in feces and urine. Enzymatic hydrolysis of POM ester to the parent acid in intestinal tissue was faster for a more lipophilic ester. Hydrolytic activity, which was detected in the content of the intestinal lumen, would lower the absorption. The effect of the C-3 substituent on water solubility was not important for the absorption of cephalosporin employed in the present study. Isomerization of the double bond, which was found to be characteristic for cephalosporin ester, presented a problem in the prodrug approach for oral use.

Animals↗
PubMed1989

Spontaneous and luminol-dependent chemiluminescences from tissue preparations of benzo[a]pyrene-injected mice.

Chemiluminescence (CL) from tissue preparations of mice i.p. injected with and without the chemical carcinogen benzo[a]pyrene (BP) was detected by a single photon counting apparatus. The spontaneously emitted CL (spontaneous CL) and the CL after luminol addition (luminol-CL) were measured for mice with and without previous induction of their liver mixed-function oxidases (MFO) by phenobarbital. In MFO-non-induced mice, although the spontaneous CL was not notably modified by BP injection, the kidneys presented three times greater luminol-CL after BP injection. On the other hand, MFO-induced mice had higher spontaneous CL of plasma, liver, kidneys, and lungs, as well as higher luminol-CL of liver after BP injection, when compared with the respective MFO-induced but BP-non-injected mice. The luminol-CL of liver was suppressed by scavengers of active oxygen and free-radicals such as TIRON, butylhydroxytoluene and in a less extent by superoxide dismutase. The CL detected from tissue preparations of mice after BP treatment is thought to reflect the formation of oxygen radicals and electronically excited-species during BP metabolism.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMed1989

[Neoadjuvant chemoradiotherapy in locally invasive transitional cell carcinoma of the urinary bladder: early results of PVB and CAP therapy].

A total of 22 patients with locally invasive transitional cell carcinoma of the urinary bladder were treated with neoadjuvant cis-diamminedichloroplatinum (CDDP), vincristine, peplomycin (PVB) or cyclophosphamide, doxorubicin, CDDP (CAP) combined with radiation therapy in our institutes between June, 1982 and May, 1988. Twelve patients were entered into the PVB regimen and the remaining 10 patients into the CAP regimen. In the PVB treated group, clinical response was obtained in 2 complete response (CR) and 6 partial response (PR), 8 out of 12 patients (66.7%). Downstaging was noted in 8 out of 12 patients (66.7%). In the CAP treated group, a clinical response was obtained in 1 of CR and in 2 of PR out of the 9 patients with evaluable lesions (33.3%). Downstaging was noted in 6 out of 9 patients (66.7%). There were no significant side effects in either the PVB or CAP treated groups, and these neoadjuvant therapies were well-tolerated. These results indicated that neoadjuvant PVB or CAP combined with radiation therapy would be useful in the management of invasive bladder cancer.

Aged↗
PubMed1989

Surface views of nuclear pores in isolated rat liver nuclei as revealed by fracture-flip/Triton-X.

We report here the use of fracture-flip (Anderson Forsman, C., P. Pinto da Silva, J. Cell Sci. 90, 531-541 (1988] and fracture-flip/Triton X-100 to examine the cytoplasmic surface of the outer nuclear membrane, and the perinuclear (exoplasmic) surface of the inner nuclear membrane of rat liver nuclei. After freeze-fracture, carbon stabilization and thawing, unfixed nuclei were treated with Triton X-100 to dissolve unfractured portions of the outer nuclear membrane. Flipping of the casts with their carbon-stabilized membrane halves (cytoplasmic half of the outer nuclear membrane; exoplasmic half of the inner nuclear membrane) exposed the cytoplasmic surface of the outer nuclear membrane and the surface of the inner nuclear membrane facing the perinuclear space. After drying, these membrane surfaces were visualized by Pt/C shadowing. We show that the cytoplasmic surface of outer nuclear membrane is covered by numerous large, oblong "kernel-like" globular particles (30-35 nm length, 25-30 nm width), often aligned into curved chains or grouped into clusters. Because of their size and characteristic arrays, we interpret these particles as ribosomes. Over the cytoplasmic surfaces of the outer nuclear membrane the nuclear pore complexes (outer diameter: 120-130 nm) appear as relatively inconspicuous annular structures, only slightly raised against the surrounding areas of membrane surface. Observation of the surface of the inner nuclear membrane facing the perinuclear space reveals prominent, sharply raised, "doughnut-like" nuclear pore complexes (outer diameter: 120-130 nm; inner diameter: 40 nm). Our results indicate the absence of large, protruding, ribosome-like structures lining the nuclear pore at its cytoplasmic surface, as proposed before.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

[Ultracytochemical study of Ca++-ATPase activity in rabbit trabecular meshwork].

Cytochemical localization of Ca++-ATPase activity in endothelial cells of rabbit trabecular meshwork was studied by the method of Ando et al. Ca++-ATPase activity was localized on the plasma membrane, mitochondria, endoplasmic reticulum, and the basal cytoplasmic matrix, which includes the actin filament bundles beneath the basal plasma membrane. Ca++-ATPase activity associated with membranous organelles was considerably reduced by quercetin, an inhibitor of ATP dependent Ca++-transport. Changes in the concentrations of Ca (1-10mM) greatly influenced the activity of the cytoplasmic matrix. The most intense activity was obtained at 1mM Ca. These findings suggest that Ca++-ATPase of mitochondria and sarcoplasmic reticulum is related to the active uptake of Ca++ by these structures, and the reaction within actin filament bundles may reflect actomyosin ATPase activity. The function of cAMP and actomyosin ATPase reaction may be to provide contractility of the trabecular meshwork resulting in an alteration of outflow resistance of aqueous humor drainage.

Animals↗
PubMed1989

[Two types of relaxation responses mediated by cyclic GMP in cerebral arteries].

It has been reported that endothelium-derived relaxing factor (EDRF) possesses chemical and pharmacological properties that are indistinguishable from those of nitric oxide (NO). Moreover, NO is the active chemical species responsible for endothelium-independent vasodilation produced by nitrogen oxide-containing substances including glyceryl trinitrate (GTN). Both EDRF and GTN activate soluble guanylate cyclase and consequently increase cyclic GMP level in various artery preparations. However, there have been few reports regarding cyclic GMP accumulation induced by EDRF or GTN in canine cerebral arteries. Therefore, it was investigated whether EDRF and GTN cause vasodilation through the common pathway mediated by cyclic GMP in the canine basilar artery. The relaxation responses induced by EDRF or GTN were studied in the canine basilar artery by an isometric tension-recording method. EDRF was induced by calcium ionophore A 23187. A 23187 did not relax the vascular tissue in the absence of the endothelial cells. On the other hand, GTN did induce relaxation in either the presence or absence of endothelial cells. FeSO4 at 3 X 10(-5) M reversed A23187-induced relaxation, but not GTN-induced relaxation (N = 10). Since Fe2+ is able to catalyse the formation of O2- in oxygenated phosphate buffer, these findings suggest that Fe2+ antagonizes EDRF by inactivating it via the generation of O2-. By the addition of 10(-5) M methylene blue, both A 23187- and GTN-induced relaxations were reversed (N = 8). Moreover, pretreatment with 10(-5) M methylene blue augmented contractile responses to 3 X 10(-6) M prostaglandin F2 alpha (N = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Fatal graft-versus-host disease following transfusion during open heart surgery.

We report fatal transfusion-associated graft-versus-host disease (GVHD) in a patient who was not severely immunosuppressed. A 58-year-old man received 800 ml of fresh whole blood from his son and an unrelated volunteer donor during open heart surgery. On the 10th day after the operation, he suddenly had a high fever, followed by generalized skin rash and liver dysfunction. Pancytopenia due to bone marrow aplasia developed a week later. A skin biopsy revealed a cutaneous lesion highly compatible with acute GVHD. The patient did not respond to high-dose methylprednisolone therapy, and died of multiple organ failure on the 18th day after the operation.

Graft vs Host Disease↗
PubMed1989

[Relapse of gingival tumor during hematological remission in acute promyelocytic leukemia].

A 56-year-old man was admitted to the hospital in April, 1986, with the chief complaint of fatigue. The diagnosis of acute promyelocytic leukemia (APL) was made based on the proliferation of atypical promyelocytes in the bone marrow. No gingival swelling was found on admission. A complete remission was achieved by the BHAC-DMP therapy and maintained by the consolidation therapy and the intensification therapy. In July, 1987, he noticed a solitary gingival tumor around the left lower second molar. The biopsy showed the massive infiltration of leukemic cells, despite the hematological remission. Combination chemotherapy was not effective but the tumor disappeared by irradiation. A hematological relapse occurred in November, 1987, but the second complete remission was achieved by the AB-triple V therapy. He died because of the second hematological relapse in July, 1988. Along with the wide use of intensive chemotherapy for acute leukemia, tumor forming leukemia during the hematological remission, as seen in this case, would be increasing. Thus, we should not overlook any newly formed tumor in the treatment of leukemia.

Aclarubicin↗