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Biomedical subjects

M Fukuda

Publications and source records attributed to M Fukuda.

At least 505 records · Page 28Linked to original sources

[Efficacy of lidocaine tape for venous cannulation in children].

We evaluated whether lidocaine tape (3 X 5 cm, contained 18 mg of lidocaine) could reduce pain caused by venous cannulation in children during anesthetic induction. One hundred and thirty-five children scheduled for elective surgery were randomly assigned to three groups according to the application time of the tape (30 min, 60 min and 120 min). Pain assessment was made by using our pain score (0: no response, 1: slight agitation, 2: strong agitation, at the venous cannulation). The effect of pain reduction (pain score 0 and 1) was found in 81 % of all patients. Especially in the group of 120 min, the effect was remarkable. Only 6.7% of all patients had slight adverse effects including skin redness and itching. In another 25 patients (weighing 3.5-30 kg), plasma concentration of lidocaine were measured 120 min after application of a piece of this tape. Arterial blood was sampled at 30 and 120 min after the tape was removed. Plasma lidocaine levels were always below 0.8 mcg.ml-1 In conclusion, the lidocaine tape may be useful and safely applicable for venous cannulation in children.

Administration, Cutaneous↗

[A case of retinal detachment in Kniest dysplasia treated with vitreous surgery].

We report a case of retinal detachment with Kniest dysplasia for which vitreous surgery was effective. The patient was a 7-year-old female who had the typical ocular and physical findings of this disease. Visual acuity was light perception alone due to a hypermature cataract and bullous retinal detachment. We performed cataract surgery and pars plana vitrectomy, and used silicone oil tamponade. After seven months, the silicone oil was removed, and visual acuity improved to 0.09. We conclude that bullous retinal detachment with Kniest dysplasia can be treated by vitreous surgery in combination with the use of silicone oil tamponade.

Abnormalities, Multiple↗

Potential role of streptozotocin in enhancing ossification of the posterior longitudinal ligament of the cervical spine in the hereditary spinal hyperostotic mouse (twy/twy).

We investigated the effects of streptozotocin-induced diabetes mellitus on ossification of the posterior longitudinal ligament (OPLL) in the murine cervical spine. A genetically-bound spinal hyperostotic mouse, the tip-toe walking Yoshimura (twy) mouse, was used in these experiments. Histological examination showed that streptozotocin enhanced membranous and enchondral ossification of the posterior longitudinal ligament of the cervical spine, particularly in the area of the ligamentous enthesis. It also increased the number of alkaline phosphatase-positive osteoblast-like mesenchymal cells particularly around the enthesis, while the number of such cells was less in control twy mice and ICR mice treated with streptozotocin. The area of OPLL subsequently increased in size in streptozotocin-treated twy mice. We suggest that streptozotocin-induced diabetes enhances OPLL in the genetically-bound spinal hyperostotic mouse (twy/twy).

Age Factors↗

[Relationship between streptomycin susceptibility and rpsL mutations of Mycobacterium tuberculosis strains].

The relationship between streptomycin (SM) susceptibility and rpsL mutations of Mycobacterium tuberculosis strains was studied. Of 18 clinically isolated SM-resistant M.tuberculosis strains, mutation was suspected in 9 strains (50%) with SM MICs of > or = 256 micrograms/ml by PCR-single strand conformation polymorphism targeting rpsL gene. On the other hand, using PCR-direct sequence method, amino acid substitution caused by single nucleotide point mutation in rpsL gene was demonstrated in 11 out of 18 strains (61%). The same amino acid substitution at codon 43 (Lys-->Arg) was observed in all 11 strains with SM MICs of > or = 256 micrograms/ml. In addition, PCR products obtained from these 11 strains could not be cut by a restriction enzyme, Mbo II, while H37Rv strain and the other 32 strains with SM MICs of < 256 micrograms/ml were cut into 2 fragments. In conclusion, our results suggest that highly SM-resistant M.tuberculosis strains with MICs of > or = 256 micrograms/ml could be rapidly and easily detected by the restriction enzymatic method.

Antibiotics, Antitubercular↗

[Congenital mid-ureteral stricture: report of a case].

A rare case of congenital mid-ureteral stricture is reported. A 17-year-old woman was admitted with sudden onset of right flank pain. Intravenous urography demonstrated bilateral small renal calculi, left hydronephrosis and a stricture of the left ureter at the level of the pelvic brim. The diagnosis was determined as congenital mid-ureteral stricture because the ureter tapered smoothly from 25 mm to 5 mm in diameter at the stenotic site. She was successfully treated by partial ureterectomy with end-to-end anastomosis. Histopathologically, no dysplasia of muscular layer was recognized.

Adolescent↗

[Elucidation of the mechanism of retinal degeneration and regeneration and the prospects for its clinical application].

In order to obtain the basic knowledge necessary to develop therapeutical intervention for blindness due to the damaged retina and optic nerve, the mechanism of retinal degeneration and regeneration in an amphibian model, Cynops pyrrhogaster, was studied. In the retinal degenerative process following enucleation and reimplantation of the eye ball, evidence was found for active cell death of neural retinal cells. As the degeneration proceeded, Musashi, an ribonucleic acid (RNA)-binding protein, started its expression in the daughter cells of proliferating retinal pigment epithelium (RPE) cells, messenger RNA (mRNA) expression of proneural genes with basic helix-loop-helix motif was then detected in the newly developing retina. These results suggest that transdifferentiation of RPE cells to neural retina involves at least partial cascade, if not entirely, of neural induction from uncommitted ectodermal tissue. Search for genes that are required for transdifferentiation of RPE cells to neural retinal cells, in addition to those mentioned above, will provide the basic knowledge for successful retinal transplantation and retinal regeneration in higher vertebrates.

Amphibians↗

Herniated cervical intervertebral discs: histological and immunohistochemical characteristics.

We examined the histological and immunohistochemical changes within and around herniated cervical intervertebral discs. A total of 28 herniated discs were harvested en bloc during anterior decompressive surgeries and examined together with the surrounding tissues. The presence of herniated discs correlated with the degeneration of cartilaginous endplate and torn annulus fibrosus. Formation of new blood vessels around the herniated discs was detected, using von Willebrand factor antibody, in seven (25% of all) uncontained hernias and eight (38%) contained hernias. Immunohistochemical studies using specific antibodies showed the presence of cells positive for matrix metalloproteinase-3 (chondrocytes), CD68 (macrophages and monocytes), and interleukin-1 beta (endothelial cells), in cervical disc hernias. Our results suggested that the magnitude and degree of immunohistochemical tissue reaction in cervical disc herniation correlate with the extent as well as location of herniated disc material.

Adult↗

[Pharmacokinetic and clinical evaluation of cefozopran in newborn patients].

Pharmacokinetic and clinical evaluation of an injectable cephem antibiotics, cefozopran (SCE-2787, CZOP), was conducted in newborn patients and the following results were obtained: 1. Clinical results The clinical efficacy of CZOP was evaluated in one each patient with intrauterine infection and suspected septicemia. The efficacy was "excellent" in both patients. No clinically serious adverse drug reactions of signs and symptoms and abnormal alterations of the laboratory test values were recognized. 2. Pharmacokinetics CZOP was intravenously given to newborn patients at doses of 25.0, 20.0, and 18.75 mg/kg. The blood CZOP concentrations were 44.7 +/- 7.0 micrograms/ml (n = 3), 48.3 micrograms/ml and 48.2 micrograms/ml at one hour after administration, respectively. The elimination half life (T 1/2) was 4.22 +/- 1.17 hours (n = 3) in the patients given 25.0 mg/kg and 2.74 hours in the patient given 20.0 mg/kg. The urinary drug excretion rate was 44.5 +/- 8.7% and 31.3 +/- 9.7% of dose within 8 hours after administration of 25.0 mg/kg and 20.0 mg/kg, respectively.

Bacterial Infections↗

An inhibitory effect of actin on casein kinase II activity in vitro.

The inhibitory effect of actin on protein phosphorylation by three distinct protein kinases (CK-II, A-kinase and MAP-kinase) was examined in vitro. It was found that: (i) actin inhibits the activities of alpha-monomeric CK-II (CK-IIalpha) as well as oligomeric CK-II (alpha2beta2) in a dose-dependent manner, but has no effect on the activities of the two other kinases; and (ii) actin-induced inhibition of CK-II activity is due to the binding of actin to the alpha-subunit of CK-II and is non-competitive with its phosphate acceptors. In addition, it is demonstrated that actin binds directly to CK-II: both actin and CK-II are coprecipitated by anti-serum against Drosophila CK-IIbeta or by specific IgG against Ascaris suum muscle actin. The results presented here suggest that actin can suppress CK-II-mediated signal transduction.

Actins↗

Mutation of the pleckstrin homology domain of Bruton's tyrosine kinase in immunodeficiency impaired inositol 1,3,4,5-tetrakisphosphate binding capacity.

Bruton's tyrosine kinase (Btk), a cytoplasmic protein-tyrosine kinase, plays a pivotal role in B cell activation and development. Mutations in the pleckstrin homology (PH) domain of the Btk gene cause human X-linked agammaglobulinemia (XLA) and murine X-linked immunodeficiency (Xid). In this paper, we report that the PH domain of Btk functions as an inositol 1,3,4,5-tetrakisphosphate (IP4), inositol 1,3,4,5,6-pentakisphosphate, and inositol 1,2,3,4,5,6-hexakisphosphate (IP6) binding domain (Kd of approximately 40 nM for IP4), and that all of the XLA (Phe replaced by Ser at position 25 (F25S), R28H, T33P, V64F, and V113D) and Xid mutations (R28C) found in the PH domain result in a dramatic reduction of IP4 binding activity. Furthermore, the rare alternative splicing variant, with 33 amino acids deleted in the PH domain, corresponding to exon 3 of the Btk gene, also impaired IP4 binding capacity. In contrast, a gain-of-function mutant called Btk*, which carries a E41K mutation in the PH domain, binds IP6 with two times higher affinity than the wild type. Our data suggest that B cell differentiation is closely correlated with the IP4 binding capacity of the PH domain of Btk.

Agammaglobulinaemia Tyrosine Kinase↗

6'-Sulfo sialyl Lex but not 6-sulfo sialyl Lex expressed on the cell surface supports L-selectin-mediated adhesion.

In order to determine if a sulfated oligosaccharide on the cell surface can function as an L-selectin ligand, a novel approach for in vitro transfer of oligosaccharides was utilized (Srivastava, G., Kaun, K. J., Hindsgaul, O., and Palcic, M. M. (1992) J. Biol. Chem. 267, 22356-22361). CHO cells were incubated with synthetic 6'-sulfo sialyl Lex, NeuNAcalpha2-->3(sulfate-6)Galbeta1-->4(Fucalpha1-->3) GlcNAc or 6-sulfo sialyl Lex, NeuNAcalpha2-->3Galbeta1-->4[(Fucalpha1-->3)sulfate--> 6GlcNAc] oligosaccharide linked to C-6 of a fucose residue in GDP-fucose and a milk fucosyltransferase. The resultant CHO cells expressing 6'-sulfo sialyl Lex or 6-sulfo sialyl Lex on their cell surface were tested for adhesion to E-selectin and L-selectin chimeric proteins coated on plates. The results indicate that 6'-sulfo sialyl Lex supports L-selectin-mediated adhesion much better than sialyl Lex similarly tagged on the cell surface. In contrast, 6-sulfo sialyl Lex containing a sulfate group on the N-acetylglucosamine residue did not support adhesion with either selectin. These combined results suggest that 6'-sulfo sialyl Lex is a much better ligand than sialyl Lex oligosaccharide for L-selectin.

Animals↗

Cytoplasmic localization of mitogen-activated protein kinase kinase directed by its NH2-terminal, leucine-rich short amino acid sequence, which acts as a nuclear export signal.

Mitogen-activated protein kinase (MAPK) is activated in cytoplasm in response to extracellular signals and then is translocated to nucleus. A directed activator for MAPK, MAPK kinase (MAPKK), stays in cytoplasm to transmit the signal from the plasma membrane to MAPK. Here we show that MAPKK contains a short amino acid sequence in the N-terminal region (residues 32-44), which acts as a nuclear export signal (NES) and thus is required for cytoplasmic localization of MAPKK. This NES sequence of MAPKK, like that of protein kinase inhibitor of cAMP-dependent protein kinase or Rev, is rich in leucine residues, which are crucial for the NES activity. Furthermore, the NES peptide of protein kinase inhibitor, as well as the NES peptide of MAPKK, inhibited the nuclear export of ovalbumin conjugated to the NES peptide of MAPKK. These results may suggest a common mechanism of nuclear export using a general leucine-rich NES.

Amino Acid Sequence↗

Structure-function relationships of the mouse Gap1m. Determination of the inositol 1,3,4,5-tetrakisphosphate-binding domain.

Gap1(IP4BP), one of a member of Ras GTPase-activating proteins, has been identified as a specific inositol 1,3,4,5-tetrakisphosphate (IP4)-binding protein (Cullen, P. J., Hsuan, J. J., Truong, O., Letcher, A. J., Jackson, T. R., Dawson, A. P., and Irvine, R. F. (1995) Nature 386, 527-530). In this paper we describe Gap1(m), which is closely related to Gap1(IP4BP), to also be an IP4-binding protein and show that the pleckstrin homology domain (PH) is the central IP4-binding domain by expressing fragments of the mouse Gap1(m) in Escherichia coli as fusion proteins and examining their activities. However, in addition to the PH domain, an adjacent GAP-related domain and carboxyl terminus are required for high affinity specific IP4 binding. The PH domain is highly conserved in the Gap1 family and also has striking homology to the amino-terminal region of Bruton's tyrosine kinase. Substitution of Cys for Arg at position 628 in the PH domain corresponding to the mutation of Bruton's tyrosine kinase observed in X-linked immunodeficiency mice results in a dramatic reduction of IP4 binding activity as well as phospholipid binding capacity of Gap1(m). This mutant also showed the GAP activity against Ha-Ras to be similar to that of the wild type Gap1(m). Our results suggest that the PH domain of Gap1(m) functions as a modulatory domain of GAP activity by binding IP4 and phospholipids.

Amino Acid Sequence↗

Natural resistance against tumors grafted into the brain in association with histocompatibility-class-I-antigen expression.

The role of MHC-class-I-antigen expression in intracerebral anti-tumor natural resistance was examined using MHC-positive Lym+ and MHC-negative Lym- lymphoma cell lines. Lym+ was sensitive to MHC-class-I-restricted CTL-mediated lysis, while lym- was resistant. Both lines were susceptible to NK-cell-mediated lysis. There was no difference in in vitro growth rate of in vivo intraperitoneal tumorigenicity between them. Inoculation of Lym+ cells into the brain caused upregulation of the intracellular MHC mRNA to the same level as after treatment with interferon-gamma, resulting in an increase in cell-surface MHC expression. Although inoculated Lym- cells also underwent an increase in cytosolic MHC mRNA, the cell-surface MHC expression remained negative. Immunoprecipitation revealed that the terminal glycosylation did not occur normally in Lym-. An in vivo intracerebral tumorigenicity assay, using 2 groups of untreated and NK-cell-depleted syngeneic mice, showed that Lym+ was less tumorigenic than Lym-. In T-cell-depleted mice, however, no difference was detected between them. In addition, when Lym+ and Lym- cells were inoculated into the brain of allogeneic or syngeneic preimmunized mice (immunized with tumor cells), Lym+ was rejected, while Lym- was accepted. When allogeneic mice had received treatment for T-cell depletion before intracerebral inoculation, no rejection was observed in Lym+. On the other hand, Lym- cells, when injected i.p. into NK-depleted mice, had greater killing activity than Lym+ cells, while in T-cell-depleted mice Lym- was less tumorigenic than Lym+. These results suggest that MHC-positive tumor cells grafted into the brain may be rejected by CTL in an MHC-dependent manner, whereas MHC-negative tumor cells can escape from T-cell-mediated immunosurveillance and grow progressively in the brain, due to absence of intracerebral natural resistance mediated by NK cells.

Animals↗

Lysosome-associated membrane proteins h-LAMP1 (CD107a) and h-LAMP2 (CD107b) are activation-dependent cell surface glycoproteins in human peripheral blood mononuclear cells which mediate cell adhesion to vascular endothelium.

Lysosome-associated membrane proteins (LAMPs) are transmembrane lysosomal glycoproteins which are detectable at the cell surface of lymphocytes in patients with scleroderma and systemic lupus erythematosus. While these proteins have been shown to mediate adhesion of tumor cells to vascular endothelial selectins, the function of LAMPs expressed at the cell surface of peripheral blood lymphocytes has not been previously examined. In the present study, the role of lamp2 (CD107b) in lymphocyte adhesion to vascular endothelium and the factors which influence in vitro cell surface expression of both lamp1 (CD107a) and lamp2 (CD107b) are examined. Freshly isolated PBMCs and unstimulated PBMCs in the culture had low levels of cell surface lamp1 and lamp2 expression which were significantly increased following PHA stimulation (P < 0.0001). A dose-dependent response to PHA and the effect of varying concentrations of serum were defined. Kinetic analysis revealed that the majority of the increase in both lamp1 and lamp2 occurred within the first 2 hr of incubation and that a subset of PBMCs maintained expression for at least 96 hr. Incubation of cells with colchicine and cycloheximide modified the cell surface expression of these proteins. Interleukins 2, 4, 6, and 8 had only a modest effect on the degree of cell surface lamp1 and lamp2 expression, though they did significantly affect the distribution of expression among different subtypes of lymphoid cells. Under the conditions utilized in this study, cell surface LAMP expression was confined primarily to CD56+ cells and to CD3+ cells. Functional analysis utilizing a fluorescence-based adhesion assay revealed that cell surface lamp2 mediates adhesion of PBMCs to vascular endothelium, possibly by interacting with endothelial selectins. LAMPs likely contribute to the migration of activated leukocytes to sites of inflammation in vivo.

Adult↗

Plasma vanillylmandelic acid level as an index of psychological stress response in normal subjects.

The relationships between psychological stress responses and plasma levels of vanillylmandelic acid (VMA), 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindolacetic acid (5-HIAA) were investigated in normal volunteers. Two questionnaires were used to measure stress: the Psychological Stress Response Scale (PSRS) and the State-Trait Anxiety Inventory (STAI). Plasma levels of VMA--but not MHPG, HVA, and 5-HIAA--showed significant positive correlations with PSRS emotional and cognitive-behavioral stress and STAI state anxiety. Significant positive correlations were also found between plasma levels of VMA and MHPG and psychological stress responses measured repeatedly in a longitudinal study of an Olympic swimmer. Plasma VMA measurements, which reflect the level of activity of the peripheral sympathetic nervous system, may provide a useful biochemical index of psychological stress responses in normal subjects.

Adult↗

Sterol 14-demethylase P450 activity expressed in rat gonads: contribution to the formation of mammalian meiosis-activating sterol.

Sterol 14-demethylase P450 (P45014DM)-dependent formation of 4,4-dimethylcholesta-8,14,24-trienol, that has been reported for a mammalian meiosis-activating sterol, in rat ovaries was confirmed. Transient elevation of ovarian P45014DM activity, that might be related to the female sexual cycle of rat, was observed. The P45014DM activity of immature ovaries was induced by pregnant mare's serum gonadotropin. These facts suggest the contribution of ovarian P45014DM to the gonadotropin-dependent formation of the meiosis-activating sterol, and provide a clue to understanding the mechanism how gonadotropins initiate the resumption of meiosis of mammalian oocytes. It was also found that rat testicular P45014DM participated in the production of 4,4-dimethylcholesta-8,24-dienol that was reported for another meiosis-activated sterol isolated from bull testes.

Animals↗