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Biomedical subjects

T Fujikawa

Publications and source records attributed to T Fujikawa.

At least 37 records · Page 2Linked to original sources

Sb K-edge absorption fine structure of Sb2Te3.

In order to study the local structure of some antimony compounds, Sb K-edge XAFS spectra were measured for Sb2Te3 and InSb. The measurements were performed in the transmission mode at BL-01 of SPring-8. Though crystal structure of antimony telluride Sb2Te3 is known by X-ray diffraction analysis, the EXAFS analyses give controversial result on the Sb-Te distance and the coordination number of Sb2Te3. Comparing the observed XANES spectra for Sb2Te3 with FEFF8 calculation, we can explain the controversial results which are also supported by the observed X-ray powder diffraction.

Journal Article↗

Multiple scattering approach to K-edge XANES of Sb-Te systems.

The Sb-Te systems are important for optical memories. The local structures of these Sb-Te systems are crucial to understand the properties. Here we study three different Sb-Te systems, Sb2Te3, c- and a-SbTe (c; crystalline, a; amorphous) by use of XANES analyses. The present calculations for Sb2Te3 system show quite good agreement with the observed spectra. In contrast to Sb2Te3 system, both c- and a-SbTe systems, in which a ratio of Sb to Te is 3, are metastable; both of the structures have not been known yet. We thus investigate these local structures by use of the multiple scattering approach, and propose a possible model for each of c- and a-SbTe.

Journal Article↗

Neonatal alloimmune thrombocytopenia due to anti-human leukocyte antigen antibody: a case report.

Anti-HLA antibodies reportedly exist in 31% of pregnant women. However, few ocurrences of neonatal alloimmune thrombocytopenia (NAIT) caused by anti-HLA antibody have been reported. In this study, maternal anti-HLA B60 and B61 antibodies were identified in patient serum at birth, but no anti-platelet antibodies were present. No maternal anti-HLA A2, A24, B51, or B52 antibodies were detected in patient serum. Platelet transfusion from the third donor was effective because these platelets expressed HLA A24 and B52 but not B60 or B61. Cross-matching tests between patient leukocytes or platelets and maternal serum were strongly positive, indicating that maternal anti-HLA antibodies were responsible for NAIT. This report is the first to demonstrate NAIT probably caused by maternal anti-HLA A24 and B52.

Female↗

Efficacy of azithromycin, clarithromycin and beta-lactam agents against experimentally induced bronchopneumonia caused by Haemophilus influenzae in mice.

Azithromycin is an azalide with potent activity against Haemophilus influenzae including ampicillin-resistant strains. We evaluated the efficacy of azithromycin, clarithromycin and three beta -lactams when used for 1 day only and for 3 days for the treatment of a murine model of bronchopneumonia, using three strains of H. influenzae, two of which were ampicillin resistant. MICs of azithromycin (1-2 mg/L) and clarithromycin (4-8 mg/L) were similar for the three strains. The MICs of cefdinir and cefcapene for beta-lactamase-negative ampicillin-resistant (BLNAR) H. influenzae were 32 times higher than those for beta-lactamase-positive ampicillin-resistant and ampicillin-susceptible strains. The viable counts in the infected tissues of azithromycin-treated mice with bronchopneumonia caused by the susceptible strain TUM8, beta-lactamase-positive strain TUH36 and BLNAR strain TUH267 were less than the counts obtained with the other antibiotics used, irrespective of MIC. At a dose of 50 mg/kg, the area under the concentration curve and the half-life of azithromycin in the lungs were respectively three times higher and six times longer than those of clarithromycin. Our results indicate that azithromycin may be useful for both ampicillin-susceptible and ampicillin-resistant bronchopneumonial infections caused by H. influenzae.

Animals↗

In vitro and in vivo activities of meropenem and comparable antimicrobial agents against Haemophilus influenzae, including beta-lactamase-negative ampicillin-resistant strains.

The in vitro activity of ampicillin, cefotaxime, meropenem, panipenem, imipenem and biapenem was assayed using ampicillin-susceptible, beta-lactamase-positive and beta-lactamase-negative ampicillin-resistant (BLNAR) Haemophilus influenzae isolated recently in Japan. Against ampicillin-susceptible isolates, cefotaxime was the most potent (MIC(90) 0.016 mg/mL). Both cefotaxime and meropenem (MIC(90) of both, 0.5 mg/L) were the most potent against beta-lactamase-positive isolates. Against BLNAR isolates, meropenem (MIC(90) 0.5 mg/L) was the most potent. In murine bronchopneumonia caused by ampicillin-susceptible and BLNAR H. influenzae, cefotaxime showed the best efficacy, followed by meropenem. Our results indicate that meropenem could be a useful intravenous agent for infections caused by H. influenzae, including BLNAR strains.

Ampicillin Resistance↗

Endovascular stent grafting for the treatment of blunt thoracic aortic injury.

OBJECTIVE: Recent advances of endovascular stent-grafting (ESG) provide a new therapeutic option with minimum surgical damage for blunt aortic injury (BAI) during its acute phase. To clarify the effectiveness of ESG for BAI, a prospective clinical study at a university hospital was conducted. METHODS: All patients with blunt thoracic injury underwent thoracic contrast-enhanced computed tomographic (CT) scan. Six patients age 48.8 +/- 19.8 years, with Injury Severity Scores of 35.8 +/- 8.1, and with BAI were treated according to our protocol. The stent-graft covered by woven Dacron was placed at the injury site. Endoleakage was then checked by aortography and CT scan was again performed once a day on days 7 through 14. RESULTS: All patients had injury of the aortic isthmus. ESG placement was performed within 8 hours after injury except in one (48 hours). The operating time was 159.5 +/- 21.1 minutes and bleeding volume was 105 +/- 26.6 mL. No endoleakage was found. Repeat CT scan revealed disappearance of hematoma. All patients except one had an event-free clinical course. One patient died because of rupture of the ascending aorta on day 6; however, autopsy revealed evidence of the healing process at the injury site sealed by ESG. CONCLUSION: An ESG is a valid therapeutic option with minimal surgical invasion for patients with acute-phase aortic injury.

Adult↗

Clinical features and treatment response of patients with major depression and silent cerebral infarction.

Previously, we reported a relationship between silent cerebral infarction (SCI), as detected by magnetic resonance imaging (MRI), and late onset major depression. In the present study, we clarify the clinical features of the depressive phase of patients with major depression and SCI, and their response to antidepressant pharmacotherapy. Using clinical charts, we retrospectively examined patients with depression, who were first admitted for antidepressant pharmacotherapy. All patients were classified according to the MRI findings and the age on admission (older or younger than 50 years) into either the young SCI(-) group (n = 23), the elderly SCI(-) group (n = 27) or the elderly SCI(+) group (n = 20).The characteristics of the clinical features were evaluated at the time of admission, after 2 weeks of treatment and at the time of discharge using the Hamilton rating scale for depression (HAMD). These data were compared between each patient group. No differences in the clinical features, as evaluated by HAMD, were observed between the three groups at the time of admission. However, the mean length of treatment was significantly longer and the treatment response, as evaluated by the total HAMD score, was significantly worse in the elderly SCI(+) group than in the other two groups, when examined after 2 weeks of treatment and at the time of discharge. The elderly SCI(+) group demonstrated higher scores in feelings of guilt, suicide, retardation and hypochondriasis than the young SCI(-) group and the elderly SCI(-) group after two weeks of treatment, and higher scores in early insomnia, late insomnia, somatic anxiety and hypochondriasis at the time of discharge. Our findings suggest that while the presence of SCI does not affect the clinical features observed at the time of admission, it does affect the treatment response to antidepressant pharmacotherapy.

Adult↗

Pharmacological properties of (2R)-N-[1-(6-aminopyridin-2-ylmethyl)piperidin-4-yl]-2-[(1R)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetamide: a novel mucarinic antagonist with M(2)-sparing antagonistic activity.

We evaluated the pharmacological profiles of (2R)-N-[1-(6- aminopyridin-2-ylmethyl)piperidin-4-yl]-2-[(1R)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetamide(compound A), which is a novel muscarinic receptor antagonist with M(2)-sparing antagonistic activity. Compound A inhibited [(3)H]NMS binding to cloned human muscarinic m1, m2, m3, m4, and m5 receptors expressed in Chinese hamster ovary cells with K(i) values (nM) of 1.5, 540, 2.8, 15, and 7.7, respectively. In isolated rat tissues, compound A inhibited carbachol-induced responses with 540-fold selectivity for trachea (K(B) = 1.2 nM) over atria (K(B) = 650 nM). In in vivo rat assays, compound A inhibited acetylcholine-induced bronchoconstriction and bradycardia with intravenous ED(50) values of 0.022 mg/kg and >/=10 mg/kg, respectively. Furthermore, in dogs, compound A (0.1-1 mg/kg p.o.) dose dependently shifted the methacholine concentration-respiratory resistance curves. In mice, compound A (10 mg/kg i.v.) did not inhibit oxotremorine-induced tremor. The brain/plasma ratio (K(p)) of compound A (3 mg/kg i.v.) was 0.13 in rats; this K(p) was less than that of scopolamine (1.7) and darifenacin (0.24). The inhibition of compound A (3 mg/kg i.v.) on ex vivo binding in rat cerebral cortex was almost similar to that of NMS. These findings demonstrate that compound A has high selectivity for M(3) receptors over M(2) receptors, displays a potent, oral M(3) antagonistic activity without inhibition of central muscarinic receptors because of low brain penetration. It is well known that central muscarinic antagonists may have diverse CNS effects, and M(2) receptors regulate cardiac pacing and act as autoreceptors in the lung and bladder. Thus, compound A may have fewer cardiac or CNS side effects than nonselective compounds.

Animals↗

A biphasic regulation of receptor mRNA expressions for growth hormone, glucocorticoid and mineralocorticoid in the rat dentate gyrus during acute stress.

Acute stress increases circulating ACTH and glucocorticoid levels. The hippocampus (HIP) is a target of such stress hormones as glucocorticoid and it also expresses receptors for growth hormone (GH), particularly in the dentate gyms (DG). In order to understand the interactions between glucocorticoids and functions of GH in HIP during acute stress, the mRNA levels for GH receptor (GHR), glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) were investigated in DG in rats exposed to restraint stress in the water (RSW). Using in situ hybridization histochemistry (ISHH), high level expressions of GHR mRNA were detected in DG. These were down-regulated by 14% after 0.5 h of RSW and then up-regulated by 38% over the initial level after 4 h of RSW. This biphasic enhancement of GHR mRNA expression in DG followed the elevation of plasma glucocorticoid levels and paralleled with biphasic expressions of mRNAs for GR and MR in DG. Although circulating GH levels did not show any correlation with the hippocampal GHR mRNA expression, adrenalectomy (ADX) decreased GHR mRNA expression in DG, and the dexamethasone treatment (DEX; 20 microg/100 microl, i.p.) of ADX rats rapidly increased the GHR mRNA expression in DG. These results have suggested that the GHR mRNA expression in the DG is regulated, at least in part, by glucocorticoids and that GH may be involved in responses of the DG to acute stress.

Acute Disease↗

Multiple functional defects in peripheral autonomic organs in mice lacking muscarinic acetylcholine receptor gene for the M3 subtype.

Muscarinic acetylcholine receptors consist of five distinct subtypes and have been important targets for drug development. In the periphery, muscarinic acetylcholine receptors mediate cholinergic signals to autonomic organs, but specific physiological functions of each subtype remain poorly elucidated. Here, we have constructed and analyzed mutant mice lacking the M(3) receptor and have demonstrated that this subtype plays key roles in salivary secretion, pupillary constriction, and bladder detrusor contractions. However, M(3)-mediated signals in digestive and reproductive organs are dispensable, likely because of redundant mechanisms through other muscarinic acetylcholine receptor subtypes or other mediators. In addition, we have found prominent urinary retention only in the male, which indicates a considerable sex difference in the micturition mechanism. Accordingly, this mutant mouse should provide a useful animal model for investigation of human diseases that are affected in the peripheral cholinergic functions.

Animals↗

Path-integral approach to Debye-Waller factors in EXAFS, EELS and XPD for cubic and quartic anharmonic potentials.

In this paper thermal effects in extended X-ray absorption fine structure (EXAFS) and X-ray photoelectron diffraction (XPD) due to atomic vibration in cubic and quartic potentials are studied by use of Feynman's path-integral approach. This approach can be applied to strongly anharmonic systems where the cumulant analyses break down. It is closely related to the well known classical approach which is only valid at high temperature. The phase of the thermal factor plays an important role both in EXAFS and XPD analyses for the asymmetric potential with strong anharmonicity. At low temperature the cumulant expansion up to the second order for the thermal damping function agrees well with the self-consistent result, but up to higher orders should be taken into account for the phase function. At high temperature the result from self-consistent calculations shows the characteristic behaviour: the thermal damping function is negative in the high-k region for both strongly and weakly anharmonic systems. The cumulant approximation cannot reproduce this behaviour. For the strongly anharmonic systems the quantum result shows qualitatively different behaviour from the classical approximation at low temperature: the former does not show the negative values even in the high-k region, while the latter shows the phase inversion in the amplitude.

Journal Article↗

Synthesis and purification of a deleted human growth hormone, hGH delta 135-146: sensitivity to plasmin cleavage and in vitro and in vivo bioactivities.

Proteolytically cleaved human 22 kDa growth hormone (22K hGH) between the amino acid residues 134 and 150 by plasmin or other proteases in vitro has been reported to be most active in growth promoting activity. In this study a deleted mutant hGH lacking amino acid residues from 135 to 146 and having more sensitivity to plasmin digestion was produced using the inverse polymerase chain reaction method and the Escherichia coli expression system. The mutant, hGH delta 135-146, was folded and purified effectively and found to be more sensitive to plasmin cleavage to form the two-chain form in vitro. The biological activities of this plasmin sensitive hGH delta 135-146 were tested by in vitro cell proliferation assays and in vivo growth promoting assay. In Ba/F3-hGHR cells, which express receptors for hGH, hGH delta 135-146 showed 10-20% less growth promoting activity than 22K hGH, but expressed comparable quantities of IGF-I mRNA to that of 22K hGH. In Nb2 rat lymphoma cells, which proliferate in response to hGH via the lactogenic receptors, hGH delta 135-146 showed equivalent activities to those of 22K hGH at lower concentrations. By the body weight gain test using hypophysectomized rats, a lower dose (2.5 nmol kg-1) of hGH delta 135-146 exhibited an equivalent activity to that of wild type 22K hGH, but a higher dose (25 nmol kg-1) of the mutant showed less growth promoting activity than 22K hGH. These results indicated that the plasmin sensitive recombinant hGH delta 135-146 failed to show higher biological activity than the 22K hGH in vivo, suggesting the unsuccessful formation of the active two-chain form in vivo.

Animals↗

Relationship between seropositivity of husbands and primary cytomegalovirus infection during pregnancy.

The role of the sexual transmission of human cytomegalovirus (CMV) as a cause of congenital infection was investigated. Serum samples were collected from 756 pregnant women at 10 to 12 weeks of gestation and at 32 to 36 weeks of gestation. Serum samples were also obtained from the husbands of women who seroconverted and women who were seronegative during pregnancy. Commercially available enzyme immunoassay kits were used to detect serum IgG, IgM, and IgA antibodies against CMV. CMV from neonatal urinary specimens was isolated according to a standard tissue culture technique, using MRC-5 cells. At 10 to 12 weeks of gestation, 634 of the 756 pregnant women (83.9%) had IgG antibody to CMV. At 32 to 36 weeks of gestation, 642 of the 756 women (84.9%) had IgG antibody to CMV. A meaningful rise of serum IgG-antibody titer (seroconversion) occurred in 8 women (1.1%). CMV was isolated from the urine of an infant born to a seroconverted woman within a week after birth. The prevalence of IgG antibody to CMV was significantly higher in the husbands of women who seroconverted during pregnancy than in the husbands of the women who were seronegative during pregnancy (P < 0.01). Understanding the epidemiology of CMV is a key element in the development of strategies for the prevention of infection. The transmission of CMV by sexual contact may be important in the pathogenesis of congenital infection. Entirely new approaches to the prevention and treatment of congenital CMV infection are necessary, including antiviral interventions and the development of a vaccine strategy.

Antibodies, Viral↗

Murine fetal resorption and experimental pre-eclampsia are induced by both excessive Th1 and Th2 activation.

It has been proposed that immune responses in mammalian normal pregnancy are Th2-like, thereby protecting the fetus and placenta from being rejected. Administration of exogenous Th1 cytokines into pregnant mice is reported to induce feto-placental resorption. However, the effects of exogenous Th2 cytokines and Th2 directed responses in pregnant animals have not been well studied. In this study, we examined IL-4 and IL-12, which play decisive roles in the development of Th2 and Th1 responses, respectively, in the induction of fetal resorption and development of experimental pre-eclampsia. Transfer of either IL-4 and/or IL-12 stimulated splenocytes from BALB/C virgin female mice into BALB/C pregnant mice mated with either C57BL/6 or BALB/C male mice resulted in fetal resorption and glomerular nephritis associated with hypertension and proteinuria. In mice treated with IL-12 stimulated splenocytes, fatty liver degeneration associated with bile retention was observed. These results indicate that both excessive Th1 and Th2 activation contribute to the development of fetal resorption and pre-eclampsia, but that Th1 is critical to the development of liver degeneration.

Adoptive Transfer↗

Selenium kinetics and changes in glutathione peroxidase activities in patients receiving long-term parenteral nutrition and effects of supplementation with selenite.

Selenium (Se) is an essential trace element in humans. Patients receiving long-term parenteral nutrition (PN) are at risk for Se deficiency. We investigated changes in Se levels and glutathione peroxidase (GSH-Px) activity in serum and tissue (red blood cells, RBC) in addition to urinary excretion of Se in patients receiving long-term PN with and without Se supplementation. In patients without Se supplementation, both Se levels and GSH-Px activity in serum decreased with duration of PN. The serum Se levels were below the lower limits of the control values in 19 of 33 patients (58%) who received PN for less than 1 mo. Conversely, RBC GSH-Px activity remained at a sufficient level in 9 of 12 patients (75%) who received PN for 3-6 mo. The RBC Se levels in all of these patients were lower than the control levels. Urinary Se concentrations were significantly correlated with serum Se concentrations by linear regression analysis (r = 0.707, P < 0.05). In patients with Se supplementation, urinary Se concentrations increased exponentially with increases in serum Se levels. These findings indicate that a time lag precedes the decrease in levels of serum Se, RBC Se, serum GSH-Px, and RBC GSH-Px in patients without Se supplementation and the increase in excretion of urinary Se in patients with Se supplementation. The monitoring of not only serum Se levels but also RBC GSH-Px activity and urinary Se levels is required for optimal Se supplementation during long-term PN.

Adolescent↗