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M Nishikawa

Publications and source records attributed to M Nishikawa.

At least 145 records · Page 8Linked to original sources
PubMed2000

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1998). II. Background of patients].

Clinical background was investigated on 449 patients with urinary tract infections (UTIs) from whom 591 bacterial strains were isolated in 9 hospitals during the period from June, 1998 through May, 1999. About distribution of age and sex of patients and type of infections, among males, patients less than 50 years old were few, and uncomplicated UTIs without indwelling catheters was most frequent. Among females, patients less than 20 years old were few, and uncomplicated was most frequent. Escherichia coli was the most frequently isolated in uncomplicated UTIs, and the higher the ages of patients, the higher were became the isolation frequencies of Enterococcus faecalis, Proteus spp. and Klebsiella spp. In complicated UTIs with indwelling catheters and without indwelling catheters, the types of pathogens had no relation with ages. The complication of infections had decreased E. coli but that had increased Proteus spp., Pseudomonas aeruginosa and Staphylococcus aureus. Until last year, use of antibiotics had decreased pathogens isolated from patients with uncomplicated UTIs drastically in our study. But, pathogens isolated after antibiotics had increased in 1998. As for surgical procedures and types of causative organisms in UTIs, E. faecalis were more isolated when surgical procedures were experienced, and E. coli were more isolated when they were not in uncomplicated and complicated UTIs without indwelling catheters. In complicated UTIs with indwelling catheters, types of causative organisms had no relationship with surgical procedures.

Adult↗
PubMed2000

[Cigarette smoke-induced acute airway impairment].

Cigarette smoking has been implicated in many pulmonary disorders, including chronic bronchitis and chronic obstructive lung disease. Cigarette smoking is associated with increased airway responsiveness. Acute exposure to cigarette smoke increases airway responsiveness in a dose-dependent manner. A superoxide is involved in airway hyper-responsiveness induced by cigarette smoke, perhaps by direct toxic action. Cigarette smokers have increased numbers of neutrophils present in their lower respiratory tract. Acute exposure to cigarette smoke initiates a superoxide-dependent mechanism that, through NF-kappa B activation and IL-8 expression, induces infiltration of neutrophils into the airways in vivo. The alveolar macrophage is one potential source of NF-kappa B activation and IL-8 production after acute exposure to cigarette smoke. Manipulation of NF-kappa B by antioxidants in vivo may be useful in limiting biologic processes such as pro-inflammatory cytokine production, which may lead to neutrophil accumulation in the lung.

Animals↗
PubMed2000

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1998). III. Secular changes in susceptibility].

Susceptibilities to various antimicrobial agents were examined for Enterococcus faecalis, Staphylococcus aureus, Echerichia coli, Klebsiella spp. and Pseudomonas aeruginosa that were isolated from patients with urinary tract infections (UTIs) in 9 hospitals during June 1998 to May 1999, and the results were compared with those obtained during the same period from 1990 to 1997 in uncomplicated UTIs and complicated UTIs. Among E. faecalis strains, those with low susceptibilities to almost drugs have increased in the latest period. All 5 S. aureus strains isolated from uncomplicated UTIs were the most susceptible to gentamicin (GM). Over 50% of S. aureus strains isolated from complicated UTIs were susceptible to GM, and on the contrary the resistant strains have increased with the MIC90 of 256 micrograms/ml or above. Among S. aureus strains isolated from complicated UTIs, those with low susceptibilities to arbekacin (ABK) have increased in the latest period compared to those during period of 1996-1997, and the MIC90s of them have changed into the lower state from 1 microgram/ml in 1996-1997 to 4 micrograms/ml in 1998. S. aureus strains have continued high susceptibilities to vancomycin (VCM). The susceptibilities to minocycline (MINO) of E. coli showed MIC90: 4 micrograms/ml in 1997, but those have returned in the latest period in uncomplicated UTIs. The MIC90s of ofloxacin (OFLX) to E. coli isolated from uncomplicated and complicated UTIs have been lower 2-3 classes in the latest period than those in 1997. Among Klebsiella spp. strains isolated from uncomplicated UTIs, those with low susceptibilities to almost cephems had increased in 1997, but few of them were detected in the latest study. The sensitive strains of P. aeruginosa to almost drugs have increased during the latest period. The MIC50s of cefozopran (CZOP) and OFLX against P. aeruginosa were the best in our history. The sensitive strains of P. aeruginosa to ceftazidime (CAZ) have increased and its percentage was 30%. Piperacilline (PIPC), cefoperazone (CPZ), GM and OFLX resistant P. aeruginosa strains have increased in the latest period.

Anti-Bacterial Agents↗
PubMed2000

Cerebrospinal fluid concentrations of alpha-melanocyte-stimulating hormone in bacterial and aseptic meningitis.

UNLABELLED: alpha-Melanocyte-stimulating hormone (alpha-MSH) has potent anti-inflammatory effects in several experimental models of inflammation. It inhibits both the actions and production of proinflammatory cytokines and neutrophil migration. We investigated whether alpha-MSH in cerebrospinal fluid (CSF) increases during the acute stage in patients with bacterial and aseptic meningitis by measuring alpha-MSH in CSF via radioimmunoassay. The alpha-MSH concentrations in CSF from the children with bacterial meningitis who survived (n = 8), those with aseptic meningitis (n = 16), and the control subjects (n = 23) were all below the detection limit. However, CSF alpha-MSH was elevated in four of the five children with bacterial meningitis who had neurological sequelae. We speculate that elevated alpha-MSH levels in CSF during acute bacterial meningitis reflect negative feedback in response to severe inflammation associated with neurological sequelae induced by proinflammatory cytokines. CONCLUSION: CSF alpha-MSH is elevated in children with severe bacterial meningitis who had neurological sequelae.

Adolescent↗
PubMed2000

[Neonatal hydrocephalus-volume determinations using computed tomography].

Computed tomography potentially offers the most accurate noninvasive means of estimating in vivo volumes. Contiguous 5 and 10-mm-thick CT scans were obtained through phantom and neonatal cranium. Cross-sectional areas were calculated for each individual scan and volumes then determined with summation-of-areas technique. The indirect intracranial volume measurement technique was then used to compare hydrocephalic and non-hydrocephalic intracranial and ventricular volumes in nine neonates. Our findings show that intracranial volumes of hydrocephalic neonates with head circumference of more than 39 cm, have 1.97 times larger than control group. The ratios of lateral ventricle versus intracranial volume are 0.57 +/- 0.2 in hydrocephalic babies and 0.0062 +/- 0.001 in control babies, respectively(p < 0.005).

Brain↗
PubMed2000

[Dural arteriovenous fistulae in the anterior cranial fossa--report of three cases].

Dural arteriovenous fistulae (DAVF's) in the anterior cranial fossa are uncommon. We encountered three patients with DAVF's in the anterior cranial fossa and reviewed the pertinent literature with regard to the etiology. All patients are middle-aged males. Two of three patients had massive intracranial hemorrhage, subarachnoidal hemorrhage in one and subdural hemorrhage in the other. One patient had a ruptured middle cerebral artery aneurysm and DAVF at the anterior cranial fossa was detected only incidentally. Angiographically, blood supplies were from the bilateral enlarged anterior ethmoidal arteries. These drained into the superior sagittal sinus via dilated frontal cortical veins. In all the patients, coagulation of the fistulous connections was carried out and the postoperative courses were uneventful. Angiographies revealed complete disappearance of the DAVF's. In conclusion, compared to cases of DAVF's in the other locations, DAVF's of the anterior cranial fossa are more likely to be brought on by sudden massive intracranial hemorrhage, and should be treated, even if asymptomatic, at the time of diagnosis. Surgical obliteration of the fistulous connection is sufficient treatment for DAVF in the anterior cranial fossa. Literature review strongly suggests that DAVF's involving the anterior cranial fossa are acquired lesions.

Aged↗
PubMed2000

[The limitations of three-dimensional CT angiography (3D-CTA) in the diagnosis of cerebral aneurysms].

OBJECT: The purpose of this study is to show some limitations of 3D-CTA to diagnose cerebral aneurysms. METHODS: Sixteen saccular aneurysms less than 10 mm in diameter were included. Large and complicated aneurysms were excluded. RESULTS: Although information about perforating arteries from the posterior cerebral artery is very important for surgery of basilar bifurcation aneurysms, 3D-CTA could not delineate the perforating arteries. A small posterior communicating artery (Pcom.A.) was not detected, and it was very difficult to differentiate infundibular dilatation of the Pcom. A. from an aneurysm. A small aneurysm of the distal middle cerebral artery could not be detected. Flow direction can not be determined by 3D-CTA, and nor could the side of the neck of the anterior communicating artery aneurysm be determined. Fenestration of the anterior communicating artery and the origin of the triple anterior cerebral artery were both misdiagnosed as anterior communicating artery aneurysms. CONCLUSION: It is premature to consider 3D-CTA as a replacement for conventional angiography.

Adult↗
PubMed2000

[Perioperative evaluation of cerebral hemodynamics by transcranial Doppler ultrasonography in patient with hemolytic uremic syndrome].

Major central nervous system (CNS) complications such as seizures and coma, occur in about 30% of children with hemolytic uremic syndrome (HUS). Serious CNS involvement is associated with an increased mortality. The purpose of this study was to evaluate intracranial hemodynamics in HUS encephalopathy. We measured mean blood flow velocity and pulsatility index (PI) of the middle cerebral artery (MCA) with transcranial Doppler (TCD) in a two year-old girl with acute encephalopathy, and compared them to those in a one year-old girl with febrile convulsion incidentally complicating HUS (a disease control). In the patient with HUS encephalopathy TCD demonstrated abnormally low PI of 0.58, while the magnetic resonance imaging (MRI) and single-photon emission-computed tomography (SPECT) reveal no abnormal findings in the acute stage. The abnormal TCD findings disappeared with her recovery. In the HUS patient with febrile convulsion alone, TCD demonstrated normal maximal flow velocity and PI. Thus TCD may be useful in evaluating intracranial hemodynamics in HUS encephalopathy in the absence of MRI and SPECT abnormalities at the early stage of illness.

Blood Flow Velocity↗
PubMed1999

Inhibitory phosphorylation site for Rho-associated kinase on smooth muscle myosin phosphatase.

It is clear from several studies that myosin phosphatase (MP) can be inhibited via a pathway that involves RhoA. However, the mechanism of inhibition is not established. These studies were carried out to test the hypothesis that Rho-kinase (Rho-associated kinase) via phosphorylation of the myosin phosphatase target subunit 1 (MYPT1) inhibited MP activity and to identify relevant sites of phosphorylation. Phosphorylation by Rho-kinase inhibited MP activity and this reflected a decrease in V(max). Activity of MP with different substrates also was inhibited by phosphorylation. Two major sites of phosphorylation on MYPT1 were Thr(695) and Thr(850). Various point mutations were designed for these phosphorylation sites. Following thiophosphorylation by Rho-kinase and assays of phosphatase activity it was determined that Thr(695) was responsible for inhibition. A site- and phosphorylation-specific antibody was developed for the sequence flanking Thr(695) and this recognized only phosphorylated Thr(695) in both native and recombinant MYPT1. Using this antibody it was shown that stimulation of serum-starved Swiss 3T3 cells by lysophosphatidic acid, thought to activate RhoA pathways, induced an increase in Thr(695) phosphorylation on MYPT1 and this effect was blocked by a Rho-kinase inhibitor, Y-27632. In summary, these results offer strong support for a physiological role of Rho-kinase in regulation of MP activity.

3T3 Cells↗
PubMed1999

A spectrophotometric assay for the transphosphatidylation activity of phospholipase D enzyme.

We developed a specific spectrophotometric assay for the quantitative determination of phospholipase D-catalyzed transphosphatidylation activity. The assay measures p-nitrophenol liberated by phospholipase D-catalyzed reaction of phosphatidyl-p-nitrophenol and ethanol in an aqueous-organic emulsion system. The release of p-nitrophenol was linear to reaction time at an early stage of the reaction with phospholipase D from Streptomyces sp. In the spectrophotometric assay for the reaction with phospholipase D from Streptomyces chromofuscus, which has higher hydrolytic activity than transphosphatidylation activity, p-nitrophenol was not found. The advantages of this novel method for measuring the transphosphatidylation activity of phospholipase D are that (i) it does not use radioactive compounds, (ii) it can measure the initial velocity of the reaction, and (iii) it is rapid, easy, and accurate to perform.

Hydrolysis↗
PubMed1999

Activity of midbrain reticular formation and neocortex during the progression of human non-rapid eye movement sleep.

To clarify the neural correlates and brain activity during the progression of human non-rapid eye movement (NREM) sleep, we examined the absolute regional cerebral blood flow (rCBF) during light and deep NREM sleep and during wakefulness in normal humans using positron emission tomography with H(2)(15)O. Relative changes in rCBF during light and deep NREM sleep in comparison to the rCBF during wakefulness were also analyzed. During light NREM sleep, the rCBF in the midbrain, in contrast to that in the pons and thalamic nuclei, did not decrease when compared to that during wakefulness, whereas rCBF decreased in the left medial frontal gyrus, left inferior frontal gyrus, and left inferior parietal gyrus of the neocortex. During deep NREM sleep, the rCBF in the midbrain tegmentum decreased, and there was a marked and bilateral decrease in the rCBF in all neocortical regions except for the perirolandic areas and the occipital lobe. There have been three groups of brain structures, each representing one type of deactivation during the progression of NREM sleep. The activity of the midbrain reticular formation is maintained during light NREM sleep and therefore represents a key distinguishing characteristic between light and deep NREM sleep. Selective deactivation of heteromodal association cortices, including those related to language, occurs with increasingly deep NREM sleep, which supports the recent theory that sleep is not a global, but it is a local process of the brain.

Adult↗
PubMed1999

Pharmacokinetics of anticancer drugs, plasmid DNA, and their delivery systems in tissue-isolated perfused tumors.

To achieve an optimal chemotherapy or gene therapy against tumors or to realize rational design of delivery systems for cancer therapy, pharmacokinetic information in tumor should be obtained. A tissue-isolated tumor preparation is a useful experimental system to investigate the intratumoral disposition of drugs, carriers, and their complexes. The disposition of drugs in the solid tumor was analyzed in this system after intraarterial infusion (systemic route) or by intratumoral injection (topical route). Here the results of low-molecular weight drugs, their macromolecular prodrugs, lipid carriers like fat emulsions and liposomes, and plasmid DNA and its complexes, are addressed. Pharmacokinetic analyses in the tumor clearly indicate that the intratumoral fate of drugs and delivery systems are determined by (i) the anatomical and physiological properties of the tissue and (ii) the physicochemical characteristics of drugs and delivery systems such as molecular weight, size, lipophilicity, and electrical charge. These approaches are useful for designing and developing optimized drug delivery systems.

Journal Article↗
PubMed1999

Design of polymeric prodrugs of prostaglandin E(1) having galactose residue for hepatocyte targeting.

Based on the relationship between in vivo disposition of macromolecules and their physicochemical and biological characteristics obtained through clearance concept-based pharmacokinetic analysis, polymeric prodrugs of prostaglandin E(1)(PGE(1)) were designed stepwise and evaluated on their targeting and therapeutic efficiencies. First poly-L-lysine (PLL) and poly-L-glutamic acid (PLGA) with an ethylenediamine (ED) spacer were modified with 2-imino-2-methoxyethyl 1-thiogalactoside to obtain galactosylated derivatives. After intravenous injection in mice, Gal-ED-PLGA was selectively taken up by the liver parenchymal cells via receptor-mediated endocytosis, while Gal-PLL accumulated in the liver as well as PLL mostly due to electrostatic interaction. Although Gal-ED-PLGA showed good targeting efficacy, its PGE(1) conjugate synthesized with activated PGE(1) by carbonyldiimidazole method failed to show therapeutic effects probably due to inactivation of PGE(1) during conjugation and lack of release in the tissue. In order to overcome these problems, we next conjugated PGE(1) to galactosylated poly-(L-glutamic acid) hydrazide (Gal-HZ-PLGA) in which PGE(1) was easily coupled to Gal-HZ-PLGA via a hydrazone bond in weak acidic solution (pH 5) at room temperature. The PGE(1)-Gal-HZ-PLGA conjugate labeled with [(111)In] or [(3)H]PGE(1) rapidly accumulated in the liver parenchymal cells. In addition, the PGE(1) conjugate effectively inhibited the increase of the GPT level in plasma, while free PGE(1) indicated no therapeutic efficacy even at more than ten times higher doses, in carbon tetrachloride-induced hepatitis mice. These findings suggest potentials of polymeric targeting systems of PGE(1) to hepatocyte utilizing galactose recognition.

Alprostadil↗
PubMed1999

Mechanisms of hepatic disposition of polystyrene microspheres in rats: effects of serum depend on the sizes of microspheres.

To study the mechanisms of the hepatic disposition of polystyrene microspheres (MS), effects of serum on their hepatic disposition characteristics were investigated for MSs with particle sizes of 50 nm (MS-50) and 500 nm (MS-500) by isolated liver perfusion experiments. It was revealed that serum in the perfusate inhibited and promoted the hepatic disposition of MS-50 and MS-500 at 37 degrees C, respectively. However, pre-heating at 56 degrees C or pre-treatment with anti-C3 antibody of serum reduced the promotive effect of serum on the hepatic uptake of MS-500, suggesting that the complement system should be involved as opsonins for the hepatic uptake of MS-500. Hepatic disposition of both MSs at 4 degrees C was reduced by the addition of serum into the perfusate, which could be ascribed to the reduction of the surface hydrophobicity of MSs due to the adsorption of serum proteins onto the surface of MSs and to resultant decrease in non-specific disposition to the liver. From these results, serum was found to function both as the opsonin to enhance the hepatic uptake of MSs and as the inhibitor by reducing non-specific interaction between MSs and the plasma membrane. Whether serum promotes or inhibits the hepatic disposition of MSs would be dependent on the particle sizes of MSs.

Animals↗
PubMed1999

Synthesis of superoxide dismutase derivative that specifically accumulates in renal proximal tubule cells.

Protection of tissues from oxygen toxicity is one of the major prerequisites to aerobic life. Since a wide variety of xenobiotics with prooxidant activity is excreted by the kidney, renal tubule cells should be protected from hazardous oxygen species. Because intravenously injected Cu/Zn-type superoxide dismutase (SOD) is rapidly excreted in the urine in its intact form, effective dismutation of superoxide radicals cannot be achieved in vivo by intravenously administered SOD. To scavenge superoxide radicals and inhibit their toxic effects in and around renal tubule cells, a hexamethylene-diamine (AH)-conjugated SOD (AH-SOD) was synthesized. When injected intravenously into the rat, (125)I-labeled AH-SOD disappeared from the circulation with a half-life of 3 min and accumulated in the kidney. After 30 min of administration, more than 80% of the radioactivity derived from AH-SOD was found to localize in the kidney without being excreted in the urine. Immunohistochemical examination revealed that, 60 min after administration, the major part of AH-SOD localized in renal proximal tubule cells. Kinetic analysis using right-side-out-oriented renal brush border vesicles revealed that AH-SOD bound to their membrane surface by some mechanism which was inhibited by AH but not by heparin and albumin. These results indicated that AH-SOD rapidly underwent renal glomerular filtration, bound to apical plasma membranes of proximal tubule cells, and localized in these cells for a fairly long time without being excreted in the urine. Thus, AH-SOD might permit studies on the role of superoxide radicals in and around renal proximal tubule cells.

Animals↗
PubMed1999

Agonist-induced regulation of myosin phosphatase activity in human platelets through activation of Rho-kinase.

Human platelets contained about 15 times lower amounts of Rho-kinase than Ca2+/calmodulin-dependent myosin light chain (MLC) kinase. Anti-myosin-binding subunit (MBS) antibody coimmunoprecipitated Rho-kinase of human platelets, and addition of GTPgammaS-RhoA stimulated phosphorylation of the 130-kD MBS of myosin phosphatase and consequently inactivated myosin phosphatase. Two kinds of selective Rho-kinase inhibitors, HA1077 and Y-27632, reduced both GTPgammaS-RhoA-dependent MBS phosphorylation and inactivation of the phosphatase activity. Activation of human platelets with thrombin, a stable thromboxane A2 analog STA2, epinephrine, and serotonin resulted in an increase in MBS phosphorylation, and the agonist-induced MBS phosphorylation was prevented by pretreatment with the respective receptor antagonist. HA1077 and Y-27632 inhibited MBS phosphorylation in platelets stimulated with these agonists. These compounds also blocked agonist-induced inactivation of myosin phosphatase in intact platelets. In addition, HA1077 and Y-27632 inhibited 20-kD MLC phosphorylation at Ser19 and ATP secretion of platelets stimulated with STA2, thrombin (0.05 U/mL), and simultaneous addition of serotonin and epinephrine, whereas these compounds did not affect MLC phosphorylation or ATP secretion when platelets were stimulated with more than 0.1 U/mL thrombin. Thus, activation of Rho-kinase and the resultant phosphorylation of MBS is likely to be the common pathway for platelet activation induced by various agonists. These results also suggest that Rho-kinase-mediated MLC phosphorylation contributes to a greater extent to the platelet secretion induced by relatively weak agonists.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1999

Hepatic uptake of polystyrene microspheres in rats: effect of particle size on intrahepatic distribution.

The in vivo disposition of polystyrene microsphere (MS) with the particle size of 50 nm (MS-50) or 500 nm (MS-500) was characterized after intravenous administration to rats. A rapid elimination from systemic circulation was observed for both MSs. Tissue distribution of MS-50 and MS-500 at 1 h after intravenous injection indicated that both MSs were exclusively distributed to liver and that small but significant amounts of MS-50 and MS-500 were also distributed to lung and spleen, respectively. To investigate the intrahepatic distribution of MS, liver was separated into liver parenchymal cells (PC) and non-parenchymal cells (NPC) at 1 or 6 h after intravenous administration. The contribution of each cell fraction was dependent on both the size of MS and the time after administration. Furthermore, by separating the NPC into endothelial cells and Kupffer cells using a centrifugal elutriation method, their contribution was also evaluated. For both MSs, Kupffer cells were recognized to be mostly responsible for the hepatic uptake, although a significant amount of MS-50 (about 28% of total uptake) was taken up by PC. On the other hand, there was little contribution of PC (about 5%) to the hepatic uptake of MS-500. The endothelial cells were contributed larger to the uptake of MS-500 (about 24%) than that of MS-50 (13%).

Animals↗