Usefulness of three dimensional ultrasonography for invisible fundus.
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Adult↗
Biomedical subjects
H Kawashima
Publications and source records attributed to H Kawashima.
Role of E-selectin in bleomycin induced lung fibrosis in mice.
BACKGROUND: Bleomycin (BLM), a well known anti-cancer drug, often causes acute lung injury and fibrosis by mechanisms that are not well understood. It is suspected that some proteases and active oxygen species generated from inflammatory cells cause the lung injury and subsequent lung fibrosis. It was therefore hypothesised that inhibition of adhesion of inflammatory cells to the endothelium might prevent these developments. METHODS: BLM (100 mg/kg) was injected into the tail veins of ICR mice to evaluate the induction of E-selectin, an adhesion molecule known to induce neutrophil attachment on endothelial cells. E-selectin mRNA induction was detected by reverse transcriptase polymerase chain reaction (RT-PCR). The myeloperoxidase (MPO) activities in the lung tissues of BLM treated and control mice were compared to evaluate neutrophil infiltration. Pathological changes in the lungs of soluble E-selectin transgenic mice (TG) and their TG negative (non-TG) littermates after BLM treatment were also compared. Serum samples of TG mice and non-TG mice were tested for their ability to block the binding of sialyl Lewis(x) to recombinant E-selectin in vitro. RESULTS: E-selectin mRNA was maximally induced at six hours after BLM treatment in the ICR mice. The soluble form of E-selectin which can competitively inhibit the binding of sialylated antigens on inflammatory cells to E- and P-selectins on the endothelium was detected in the serum of TG mice. BLM induced lung fibrosis occurred in non-TG mice but not in TG mice. This result confirms the finding that the serum of TG mice inhibits the binding of sialyl Lewis(x) to E-selectin in vitro. CONCLUSION: E-selectin plays an essential role in BLM induced lung fibrosis through the induction of neutrophil and other inflammatory cell accumulation, and soluble E-selectin may be of use in the prophylactic treatment of lung fibrosis.
Animals↗
Methotrexate concentration in cerebrospinal fluid of the space created by tumor removal.
This paper investigates the post-surgical pharmacokinetics of methotrexate (MTX) in the plasma, the cerebrospinal fluids (CSF), and the spaces created by tumor removal (STR) in patients with glioblastoma, during hyperosmotic disruption of the blood brain barrier (HODBBB) and intra-arterial chemotherapy with MTX. Eight Japanese patients with glioblastoma, three with open STRs and five with closed STRs, received a total of thirteen courses of HODBBB and intra-arterial combination chemotherapy with MTX. The patients were initially administered mannitol, then the anticancer drugs were infused into the carotid artery. Samples of blood and CSF from the STRs were obtained. MTX concentrations were measured by fluorescence polarization immunoassay and the pharmacokinetic parameters of MTX in plasma and CSF were estimated. The plasma concentrations of MTX peaked at the end of drug infusion, and then decayed bi-exponentially during the remainder of the treatment period. The CSF concentration of MTX in the STR peaked 2 h after drug administration, then mono-exponentially decreased. The area under the concentration-time curve (AUC) for plasma and CSF MTX concentrations increased in parallel with the MTX dose. In patients with open STRs, the mean AUC of MTX in CSF was 4.44% of that found in plasma, while in patients with closed STRs, the mean was 61.2% of that found in plasma. In the latter group, the MTX administered using HODBBB and intra-arterial chemotherapy was maintained in the STRs for long periods.
Area Under Curve↗
Pharmacokinetics of cytosine arabinoside, methotrexate, nimustine and valproic acid in cerebrospinal fluid during cerebrospinal fluid perfusion chemotherapy.
This report investigates the pharmacokinetics of cytosine arabinoside (Ara-C), methotrexate (MTX), nimustine (ACNU) and valproic acid (VPA) in cerebrospinal fluid (CSF) during CSF perfusion chemotherapy. A 28-year-old Japanese woman with disseminated glioblastoma was, on admission, on a stable oral regimen of prolonged-release VPA tablets (Depakene-R), 400 mg twice a day, for seizure control. Twelve courses of CSF perfusion chemotherapy with Ara-C, MTX, and ACNU were administered. Plasma samples and CSF samples via Ommaya reservoirs were obtained during the eleventh course of treatment. The Ara-C and ACNU concentrations were measured by HPLC. The MTX and VPA concentrations were measured by fluorescence polarization immunoassay. During CSF perfusion chemotherapy, the highest CSF concentrations of Ara-C, MTX, and ACNU were observed at the end of the perfusion and decreased in a monoexponential pattern. The half-lives of Ara-C, MTX, and ACNU were 2.65, 3.52, and 0.71 h, respectively. No anticancer drugs were detectable in plasma during CSF perfusion chemotherapy. Before CSF perfusion chemotherapy, the free VPA concentration in plasma was 14.4% of the total VPA concentration. The mean total and free VPA concentrations in plasma were 78.0+/-0.8 and 10.9-0.3 microg/ml, respectively. The free VPA concentrations in plasma and in CSF were of similar values. At the end of perfusion, the lowest free VPA concentration in CSF was 30.3% of that at the initiation of perfusion. The free VPA concentrations in CSF at 3, 7, 23, and 47 h after the end of perfusion were 79.8, 94.5, 100.9, and 100.9% respectively of that at the initiation of perfusion. During CSF perfusion chemotherapy, the ratio of free VPA concentrations to the total VPA in CSF was 86.3+/-6.9%. The VPA concentrations in CSF rapidly decreased during the CSF perfusion but recovered to pre-treatment levels within 7 h.
Adult↗
[1-11C]Octanoate as a PET tracer for studying ischemic stroke: evaluation in a canine model of thromboembolic stroke with positron emission tomography.
Octanoate is taken up by the brain and converted in astrocytes to glutamine through the TCA cycle after beta-oxidation. Consequently, [1-11C]octanoate might serve as a useful positron emission tomography (PET) probe for studying cerebral oxidative metabolism and/or astroglial functions. The present study attempted to evaluate the utility of using [1-11C]octanoate as a PET tracer for imaging and evaluating the pathophysiology of ischemic stroke. We used a canine model of thromboembolic stroke. Five male beagle dogs were implanted with an indwelling catheter in the left internal carotid artery. A single autologous blood clot was injected into the left internal carotid artery through the catheter. The brain distribution of [1-11C]octanoate and cerebral blood flow (CBF) were determined 24 h after insult using a high resolution PET scanner. Post mortem brain regions unstained with 2,3,5-triphenyltetrazolium chloride (TTC) were defined as infarcts. In the region of an infarct, accumulation of [1-11C]octanoate decreased concurrently with CBF reduction. In contrast, normal accumulation of [1-11C]octanoate was observed in ischemic but vital regions, suggesting that an increased accumulation of [1-11C]octanoate relative to CBF takes place in these regions. In conclusion, [1-11C]octanoate accumulated in ischemic but vital regions, indicating that [1-11C]octanoate is a potentially useful PET tracer for imaging and evaluating the pathophysiology of ischemic stroke.
Animals↗
[Repair and formation of cartilage and bone: are they possible?].
Osteoporosis and osteoarthritis cause serious problems to the mobility, and therefore to the quality of life, of aged people. This is due to the fact that both diseases result from irreversible loss of quality or function of the tissues; i.e., bone and articular cartilage. Recent progress in molecular biology and developmental biology, however, have contributed a great deal to our understanding of the mechanisms regulating growth and differentiation of osteoblasts and chondrocytes, the cells responsible for producing bone and cartilage, respectively. In vivo studies using animals including humans also shed light on the mechanism underlying these biological events as well as diseases and provide ideas for possible interventions for treating these disease states. This review will deal with these new developments in the field and discuss possibility to develop new potential strategies for treating patients with those disorders.
Animals↗
Mechanisms of [2,3-butanedione bis(N4-dimethylthiosemicarbazone)]zinc (Zn-ATSM2)-induced protection of cultured hippocampal neurons against N-methyl-D-aspartate receptor-mediated glutamate cytotoxicity.
Hyperexcitation of glutamatergic neurons may play a key role in ischemia-related neurodegeneration. Recent studies have suggested that the zinc ion (Zn2+), which is present in the central nervous system, has a modulatory role in glutamatergic neuron activity. Zinc ions block glutamate-induced depolarizing currents and neuronal damage by binding with zinc sites on the NMDA subtypes. Therefore, we examined the usefulness of zinc as a therapeutic agent for the prevention of ischemic neuronal damage in the brain. In our previous study, 2,3-butanedione bis(N4-dimethylthiosemicarbazonato) zinc complex (Zn-ATSM2), with high brain uptake, showed significant neuroprotective effects against cerebral ischemia in rats when administered systemically. In this study, to elucidate the mechanism of the neuroprotective effect of Zn-ATSM2, we first examined its in vitro protective effects against glutamate-, NMDA- and kainite-induced neurotoxicity in primary cultures of hippocampal neurons. Zn-ATSM2 elicited protective effects against this glutamate- and NMDA-induced neurotoxicity, but did not affect kainite-induced cytotoxicity. In addition, we studied the effects of Zn-ATSM2 on influx of Ca2+, which undergoes modification subsequent to NMDA activation. Zn-ATSM2 significantly decreased glutamate-induced 45Ca2+ uptake. Thus, Zn-ATSM2 protected against glutamate-induced neurotoxicity and its protective effect was, at least in part, due to the blockage of NMDA receptor-mediated Ca2+ influx.
Animals↗
Change of valproic acid concentrations during cerebrospinal fluid perfusion chemotherapy.
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Adult↗
Inhibitory effect of laidlomycin on human immunodeficiency virus replication.
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Anti-HIV Agents↗
Human leukocyte antigens in forms of leprosy among Japanese patients.
Human leukocyte antigens (HLA) class II alleles were analyzed among Japanese leprosy patients to ascertain whether immunogenetic differences exist among the leprosy classification forms of Ridley and Jopling. Ninety-three unrelated Japanese leprosy patients (21 lepromatous, 24 borderline lepromatous, 17 mid-borderline, 26 borderline tuberculoid, 5 tuberculoid) and 114 healthy control subjects were investigated. The frequencies of HLA-DRB1*1501, -DRB5*0101, -DQA1*0102 and DQB1*0602 were significantly increased in all of the Japanese leprosy patients. The frequencies of HLA-DRB1*0405, -DQA1*03 and -DQB1*0401 were significantly decreased in the Japanese patients after correction of the p value. Conversely, there were no significantly different distributions of the HLA-DRB1, -DRB5, -DQA1, DQB1 alleles in the five subgroups of these patients. We conclude that HLA class II alleles were not associated with the form of leprosy. Other HLA, a non-HLA gene, and/or environmental factors may play a critical role in the different manifestations of leprosy.
Cytotoxicity Tests, Immunologic↗
[Urethral injury with unusual clinical course: a case report].
A 20-year-old men fell from a ladder in 1995, striking his perineum strongly, and macroscopic hematuria with painful urination lasted for several days. Subsequently, swelling of the perineum on urination continued to occur. However, he did not seek medical treatment until July 1997, when he consulted our medical institution. A diverticulum-like change was found in the bulbous urethra on urethrocystography, and a tear in the same position on urethroscopy. On September 22, 1997, surgery was performed after constructing a cystostomy, the tear was located using a urethroscope, and closed through a perineal approach. At 14 days after surgery, there was extra-urethral leakage of contrast media on voiding cystourethrography, and at 28 days after surgery, the findings showed improvement. Since then, he has been free of the preoperative symptoms.
Accidental Falls↗
Sulfatide binding and activation of leukocytes through an L-selectin-independent pathway.
Sulfatide has been reported to activate leukocytes through L-selectin. Here we provide evidence that sulfatide binds to and activates leukocytes through both L-selectin-dependent and -independent pathways. Rat leukocytes of various sources shed surface L-selectin after phorbol myristate acetate (PMA) treatment, however, these cells retained the ability to bind sulfatide. In addition, sulfatide also bound to an L-selectin-negative cell line EL-4, and the binding was up-regulated by PMA. Sulfatide induced aggregation of L-selectin-positive lymphocytes, which was highly dependent on divalent cations, protein tyrosine kinases (PTK), and protein kinase C (PKC), but was independent of beta1 and beta2 integrins. In contrast, sulfatide-induced EL-4 cell aggregation required an LFA-1/ICAM-1 adhesion pathway but not PTK and PKC. A sulfatide receptor of 65 kDa was isolated from EL-4 cells. Taken together, this study suggests that sulfatide can bind to and activate leukocytes through an L-selectin-independent molecule and triggers signal transduction pathways different from those induced by L-selectin activation.
Animals↗
[Urethral diverticula surrounding the urethra in women: report of 2 cases].
We report two cases of female urethral diverticula. A 49-year-old woman (case 1) complained of perineal pain when she voided urine. A 36-year-old woman (case 2) complained of perineal pain. In both cases, intravenous pyerography and urethrography revealed diverticula around their urethra, and we diagnosed them with urethral diverticula which surrounded their urethra by magnetic resonance imaging. We treated them by transvaginal diverticulectomy. Case 2 was successfully treated, but the diverticulum recurred after one year in case 1. There are over 200 reported cases of female diverticula in the Japanese literature, but a urethral diverticulum surrounding the urethra is rare.
Adult↗
[Study on casein allergy in children].
Casein a component of milk is used for food additives, industrial materials and drugs. However casein is known to be a main allergen in milk allergy. Recently several cases of anaphylaxis to antibiotics including casein have been reported. In this study we investigated casein allergy in milk allergy. 6 out of 8 patients who were positive for milk RAST were also positive for casein RAST. In these positive cases only 3 out of 6 patients had some allergic symptoms after taking antibiotics. In 3 patients DLST was also positive to casein. There was one patient who was positive in DLST without any symptoms after taking the same antibiotics. It is needed to pay attention to casein allergy when giving the medication which includes casein.
Adolescent↗
Tensile stress induced osteoblast differentiation and osteogenesis in mouse calvarial suture in culture: possible involvement of BMP-4 and other genes.
Mechanical stress is one of the most potent inducer of bone formation. The mechanism by which cells receive and transduce the signal into osteogenesis, however, remains unknown. Previous studies have demonstrated that mechanical stress causes changes in expression levels of many genes in osteoblasts and osteocytes both in vivo and in vitro. However, none of these changes are specific to bone cells. Moreover it is not clear which types of cells contributed to the increased osteoblasts induced by mechanical stress. The purpose of this study, therefore, was to identify which cells differentiate into osteoblasts and to examine how the expression of genes that are specific to osteogenic cells changes.
Animals↗
"Decoy" of androgen-responsive element induces apoptosis in LNCaP cells.
BACKGROUND: In an androgen-dependent manner, the androgen receptor (AR) binds to the androgen-responsive element (ARE) in the regulatory region of target genes. We hypothesize that an "ARE decoy, " a double-stranded oligonucleotide containing the same DNA sequence as ARE, can inhibit prostatic proliferation by competitive inhibition of AR transcriptional activity. METHODS: We synthesized a 23-mer ARE decoy based on the deduced ARE sequence at the promoter region of the human prostate-specific antigen (PSA) gene. The nuclear extract was prepared from LNCaP cells, and DNA-protein interactions were examined by gel shift assay. Then the antiandrogen effect of the ARE decoy was studied in LNCaP cells transfected with the ARE decoy by lipofection. After 24-hr incubation with 10(-9) M dihydrotestosterone (DHT), induction of apoptosis was examined by DNA fragmentation. RESULTS: The gel shift assay demonstrated specific binding of the ARE decoy to the LNCaP nuclear protein which is most likely AR. The transfection experiment showed DNA fragmentation in the ARE decoy-transfected cells despite the presence of DHT, though not in the cells transfected with the control decoy. CONCLUSIONS: The ARE decoy had an antiandrogen effect and induced apoptosis in LNCaP cells. This ARE decoy may become a potential therapeutic tool for prostate cancers when combined with a highly efficient transfection method.
Amino Acid Sequence↗
Human prostate CYP3A5: identification of a unique 5'-untranslated sequence and characterization of purified recombinant protein.
We have isolated a cDNA clone coding for CYP3A5 from a human prostate cDNA library. The human prostate CYP3A5 cDNA had a unique 5'-untranslated sequence, suggesting that the prostate specific regulation of CYP3A5 is different from liver. Hybridization screening using a human genomic BAC library yielded four positive clones, two of which were shown to contain the unique 5'-untranslated sequence by Southern blot analysis. The CYP3A5 recombinant protein expressed in Escherichia coli using the pCWOri expression vector was purified to an almost electrophoretically homogeneous state with a specific content of 4.4 nmol of P450/mg of protein. This P450 exhibited 6beta-hydroxylation activity toward both testosterone and progesterone. No polar metabolite of 5alpha-dihydrotestosterone (DHT) was detected. The apparent K(m) values for testosterone and progesterone 6beta-hydroxylation were 143 and 114 microM, respectively, with V(max) values of 0.48 and 0. 21 nmol/min/nmol of P450, respectively. This is the first report that a particular form of P450, CYP3A5, has been isolated from human prostate and that the purified recombinant protein of CYP3A5 has been shown to be active in the metabolism of sex hormones.
5' Untranslated Regions↗