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Biomedical subjects

M Sawada

Publications and source records attributed to M Sawada.

At least 181 records · Page 10Linked to original sources
PubMed1997

Antibiotic delivery system using bioactive bone cement consisting of Bis-GMA/TEGDMA resin and bioactive glass ceramics.

A novel drug delivery system containing cephalexin (CEX) as a model drug using a new bioactive bone cement consisting of 15% bisphenol-alpha-glycidyl methacrylate (Bis-GMA), 15% triethylene-glycol dimethacrylate (TEGDMA) resin and 70% apatite- and wollastonite-containing glass-ceramic (A-W GC) powder was investigated. A-W GC powder containing CEX powder hardened within 5 min after mixing with Bis-GMA/TEGDMA resin, and furthermore its compressive strength was expected to be higher than that of polymethylmethacrylate cement. In vitro CEX release from bioactive bone cement pellets in a simulated body fluid at pH 7.25 and 37 degrees C continued for more than 2 weeks. The drug release rate increased with increasing amount of CEX in the mixture. All of the drug release profiles followed the Higuchi equation at the initial stage, but not at later stages. As hydroxyapatite was precipitated out on the cement surface, the drug release rate decreased. These results suggest that the CEX release rate from bioactive bone cement could be controlled by varying the amount of drug in the cement system.

Biomechanical Phenomena↗
PubMed1997

The influence of peri-operative blood transfusion during radical hysterectomy on the prognosis of uterine cervical cancer.

To evaluate the clinical implications of peri-operative transfusion in the surgical treatment of uterine cervical cancer, a detailed analysis of the cumulative survival rate was performed using clinical data from 145 patients with FIGO stage Ib cervical cancer of the squamous cell type acquired between 1982 and 1989 at the Center for Adult Diseases. The cumulative survival rate was statistically analyzed using the Kaplan Meier method. Of the 145 patients with stage Ib cancer, 103 were considered to have undergone complete excision and received no further treatment post-operatively, and 42 were considered to have undergone incomplete excision because of the involvement of lymph nodes or the lymphovascular space. Of the 79 patients in the former group who received peri-operative transfusion, 69 received less than seven units (1400 mL) and 10 received more than eight units (1600 mL). The cumulative 5-year survival rate was 100% in the 24 patients who received no transfusions, 91.7% in those who received less than 1400 mL, and 90.0% in those who received more than 1600 mL. Similarly, of the 42 patients in the incomplete excision group, nine did not receive any peri-operative transfusion, 27 received less than 1400 mL, and six received more than 1600 mL. The 5-year survival rate in these groups was 88.9, 77.8 and 50.0%, respectively. The survival rate of our patients with stage Ib cervical cancer without peri-operative transfusion was significantly higher than that of those with transfusion, regardless of post-operative irradiation therapy status, indicating that peri-operative transfusion has an adverse influence on the prognosis in cervical cancer.

Adult↗
PubMed1997

Inhibition of superoxide production and chemotaxis by methotrexate in neutrophils primed by TNF-alpha or LPS.

We have demonstrated recently that methotrexate (MTX) inhibits superoxide generation and chemotaxis induced by N-formylmethionyl-leucyl-phenylalanine (fMLP) in neutrophils primed by granulocyte colony-stimulating factor (G-CSF). To extend these observations, we examined the in vitro effect of MTX on fMLP-stimulated superoxide generation and chemotaxis in neutrophils primed by either tumor necrosis factor alpha (TNF-alpha) or bacterial lipopolysaccharide (LPS). MTX inhibited superoxide generation and chemotaxis more efficiently in TNF-alpha- or LPS-primed neutrophils than in unprimed neutrophils. When either hypoxanthine or guanosine was added to the culture medium, the effects of MTX were partially counteracted. Furthermore, MTX caused a significant inhibition of both superoxide production induced by phorbol 12-myristate-13-acetate and chemotaxis induced by interleukin 8 in G-CSF-primed neutrophils. These results may support the hypothesis that neutrophils primed by different stimuli are more susceptible to the inhibitory effects of MTX on superoxide generation and chemotaxis irrespective of chemoattractants. Such an effect can be partly attributed to the perturbation of purine nucleotide biosynthesis.

Cells, Cultured↗
PubMed1997

The G cell.

The study of gastrin continues to serve as an excellent model for gastrointestinal regulatory processes. This review highlights some recent advances in the field by outlining gastrin biosynthesis, summarizing current understanding of gastrin receptors, describing the regulation of gastrin release, and discussing the clinical implications of gastrin in the pathogenesis of peptic ulcer disease. Emphasis is on three emerging areas of gastrin research: the novel finding that one of gastrin's posttranslational processing intermediates has biological activity distinct from that of the mature peptide; elucidation of gastrin's signal transduction mechanisms that mediate the trophic effects of the peptide; and the role of gastrin in peptic ulcer disease pathogenesis secondary to Helicobacter pylori infection.

Animals↗
PubMed1997

Antitumor effect of CPT-11, a camptothecin derivative, on human testicular tumor xenografts in nude mice.

OBJECTIVE: The antitumor effect of CPT-11, a camptothecin derivative, on two human testicular embryonal carcinomas (TTSC-2 and TTSC-3) heterotransplanted into-nude mice was studied. MATERIALS AND METHODS: Tumor-bearing nude mice were given daily intraperitoneal injections of the anticancer drugs in 0.1 ml saline 3 times at 3-day intervals. At the end of the experiments tumors were resected and subjected to light-microscopic observation. RESULTS: When 10, 30 and 50 mg/kg of CPT-11 was administered to tumor-bearing mice intraperitoneally, the antitumor effect of CPT-11 was observed dose-dependently in both TTSC-2 and TTSC-3. When 30 mg/kg of CPT-11 was administered in combination with CDDP, complete tumor regression was observed in both TTSC-2 and TTSC-3 tumors. Histological findings correlated well with the decrease in tumor volume of treated tumors. No mice died after treatment with CPT-11 in a single-agent and combination chemotherapy. CONCLUSION: Chemotherapy with CPT-11 was an effective and safe method against human testicular tumors heterotransplanted in nude mice.

Animals↗
PubMed1997

Pathological findings of nude mice inoculated with bovine Neospora.

Nude mice were infested with bovine Neospora by intraperitoneal inoculation of the brain and spinal cord from an aborted bovine fetus due to neosporosis. Inoculated mice showed severe emaciation and tetraplegia at about 2 to 4 months post-inoculation. Histopathologically, polyradiculoneuritis and peripheral neuritis were the major findings, and lesions in the central nervous system were located at periventricular and submeningeal areas of the cerebrum or at the white matter around the roots of radices of the spinal cord. These findings may suggest the protozoa inoculated into the abdominal cavity invaded the spinal cord via the spinal nerve and later reached the brain through the cerebrospinal fluid.

Animals↗
PubMed1997

[Detection of microemboli in patients with extracranial carotid artery stenosis by transcranial Doppler sonography].

Embolism from a stenotic lesion of the extracranial internal carotid artery (ICS) is considered to be an important pathomechanism of cerebral infarction. The purpose of this study is to estimate the risk of cerebral infarction associated with microembolism in patients with ICS and thereby to determine the importance of TCD-detected microemboli in this condition. Seventy-one cases with more than 30% ICS and 10 cases without ICS were studied. TCD monitoring was carried out for an hour at the ipsilateral middle cerebral artery of each case using a 2-MHz pulse-wave transcranial Doppler device. High intensity transient signals were counted as microemboli. Microemboli were detected in 27 of 71 cases with ICS, but not in cases without ICS. Microemboli were detected more frequently in cases with 70% to 99% ICS (53.3%) compared with in cases with 30% to 69% ICS (12.5%). Cerebral infarctions were recognized in the ipsilateral hemisphere in 23 of 27 cases with microemboli (85.2%) by means of MRI. In contrast, cerebral infarctions were recognized only in 21 of 45 cases without microemboli (47.7%). These results suggest that a stenotic lesion of the extracranial internal carotid artery, especially high-grade stenosis, is a major source of cerebral embolism and that detection of microemboli by TCD is a useful tool capable of reliably assessing the risk of cerebral infarction due to ICS.

Aged↗
PubMed1997

[Smoldering leukemia with CD7.CD34(+), immunoglobulin heavy chain rearrangement (+) and hypoplastic marrow with myelofibrosis].

A 63-year-old male was admitted because of pneumonia. Peripheral blood findings showed pancytopenia with increase of blasts. A bone marrow specimen showed hypocellular marrow with increase of blasts. The blasts were positive for CD7, CD34, and HLA-DR and negative for other lymphoid antigens and myeloid antigens involving myeloperoxidase. Rearrangement of immunoglobulin heavy chain was demonstrated by Southern blotting analysis. T cell receptor beta, T cell receptor gamma and immunoglobulin light chain rearrangement were negative. A diagnosis of stem cell leukemia was made. In vitro, the blasts did not respond to recombinant human granulocyte colony-stimulating factor (rhG-CSF), cytarabine (Ara-C) and all-trans retinoic acid (ATRA). However, in the blasts of culture without cytokeins, CD33 expression was newly induced. Remission was not obtained by chemotherapies with cyclophosphamide, etoposide, prednisolone and Ara-C. Four months later, marrow specimens showed hypoplasty with myelofibrosis. One year later, the blasts showed CD33 expression with negative myeloperoxidase. The leukemia was transformed to minimally differentiated myeloid leukemia from stem cell leukemia. This condition was thought to be "smoldering leukemia" because of the slow development and refractoriness to chemotherapy. Nineteen months later the patient died due to respiratory failure by pneumonia and pulmonary bleeding despite therapy.

Acute Disease↗
PubMed1997

[Analysis of factors related to microemboli in cases with internal carotid artery stenosis].

Transcranial Doppler ultrasound (TCD) has been used to detect microemboli in cases with extracranial internal carotid artery stenosis. However, the mechanism causing microemboli has remained unclear. The purpose of this study is to clarify clinical characteristics and circumstances associated with the genesis of TCD-detected microemboli. Ninety-one cases with more than 30% stenosis of the internal carotid arteries were studied. TCD monitoring was carried out for an hour at the ipsilateral middle cerebral artery of each case using a 2-MHz pulse-wave transcranial Doppler device, and high intensity transient signals were counted as microemboli. Digital subtraction angiography, magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) were also performed in all cases. Microemboli were detected in 30 of 91 cases. Microemboli were significantly well detected in cases with a history of ischemic event and/or cerebral infarction recognized by MRI. Detection of microemboli had no relation to sex, age or clinical risk factors (hypertension, hypercholesterolemia, diabetes mellitus and smoke habituation). In contrast, detection of microemboli was significantly related to decrease in cerebral blood flow recognized by SPECT, severity of stenosis and wall irregularity of lesion recognized by angiography. Microemboli can be found in a significantly high percentage of these clinical conditions, which may be risk factors for embolic stroke caused by extracranial internal carotid artery stenosis.

Aged↗
PubMed1997

[Detection of microemboli by transcranial Doppler sonography after carotid endarterectomy].

Transcranial Doppler sonography (TCD), a non-invasive monitoring technique, has potential for detecting microemboli caused by the extracranial internal carotid artery. Many previous reports have shown that TCD-detected microemboli may be a risk factor for stroke. The main purpose of this study is to verify whether microemboli cease after carotid endarterectomy (CEA). TCD monitoring was performed in 43 cases before and after CEA. TCD monitoring was carried out for an hour at the ipsilateral middle cerebral artery of each case using a 2-MHz pulse-wave transcranial Doppler device, and high intensity transient signals were counted as microemboli. Microemboli were detected preoperatively in 10 cases (23.3%). Microemboli were not detected in any case immediately after CEA, in either the subacute stage (from 14 to 21 days after CEA) or in the chronic stage (more than 3 months after CEA). In the acute stage (from 3 to 7 days after CEA), microemboli were detected in three cases (7.0%). The rate of TCD-detected microembolic was always significantly reduced after CEA. TCD monitoring can be helpful in assessing the effect of CEA for prevention of stroke by removing the suspected source of microemboli.

Aged↗
PubMed1997

Detection of embolic signals during and after percutaneous transluminal angioplasty of subclavian and vertebral arteries using transcranial Doppler ultrasonography.

OBJECTIVE: Percutaneous transluminal angioplasty (PTA) is accepted as a safe and effective procedure for the treatment of stenotic arterial lesions of various sites. However, distal embolism may cause serious complications in the PTA of cephalic arteries. By monitoring embolic signals using transcranial Doppler (TCD) ultrasonography, we speculated regarding the safety and/or risk of PTA for vertebral and subclavian artery stenosis. METHODS: Twelve consecutive patients undergoing PTA for subclavian and vertebral artery stenosis of atherosclerotic origin were studied. All patients were refractory to initial medical treatment and were considered for PTA. During the PTA procedure, all patients were heparinized. Before, during, and after PTA, TCD monitoring was performed to detect embolic signals for 30 minutes at each time. After PTA, anticoagulant and antiplatelet therapies were continued in all patients. RESULTS: Before, during, and after PTA, a steady flow signal could be obtained from each vertebral artery monitored using TCD ultrasonography. No embolic signals were detected in any patient before angioplasty. During angioplasty, one embolic signal was detected immediately after balloon deflation in 1 of 12 patients. Several embolic signals were detected after the procedure in 6 of 12 patients, but thereafter embolic signals became less frequent in number. Three days after angioplasty, embolic signals were not detected in any patient. There were no serious complications caused by the PTA procedure. CONCLUSION: TCD monitoring may be a useful modality for detection of microemboli during and after PTA in the posterior circulation. We suspected that subclinical microemboli are released from the dilated vessels for 3 days after vertebral and subclavian PTA and that anticoagulant or antiplatelet therapies may prevent embolic complications after the procedure.

Aged↗
PubMed1997

Mechanism of intracranial rebleeding in moyamoya disease.

Intracranial hemorrhage is the major catastrophic event in the natural course of Moyamoya disease, and outcome of the patients with rebleeding is very poor. However, the mechanism underlying intracranial rebleeding is not well elucidated. We retrospectively analyzed 15 patients who bled two times or more among 46 bled patients with Moyamoya disease. The results indicated that there were two different types in the manner of rebleeding. One group consisted of seven cases, which bled two times or more at the same site than the original bleeding site. In four of these seven cases, a ruptured aneurysm was identified at the distal part of collateral vessel or on the major vessel. In the other three cases, no source of bleeding was identified. In all of these cases, rebleeding occurred within 2 months after the initial insult except for one case. Another group consisted of eight cases, which bled repeatedly but at different sites from the initial bleeding site. In any of these cases, neither aneurysms nor other vascular abnormalities were identified. In all of these cases, rebleeding occurred more than 2 months after the initial bleeding. The present result indicated that intracranial bleeding might occur as a result of rupture of a tiny aneurysm at the periphery of collateral vessels. These aneurysms may be blown out after initial bleeding. When they persist after the event, they may rupture again in a fairly short interval. In other cases, bleeding occur at different sites from the initial site. They are considered to be a result of ruptured weak Moyamoya vessels which are forced to act as collateral pathways and are under unusually increased hemodynamic stress.

Adolescent↗
PubMed1997

Clinical significance of hepatitis GB virus C infection in alcoholic liver disease.

Recently, hepatitis GB virus C (HGBV-C) has been recovered from patients with non-A-E hepatitis. However, it has been unclear whether HGBV-C may be related to the development of alcoholic liver disease (ALD) or not. In this study, we determined HGBV-C RNA in sera from alcoholic patients without markers for hepatitis C and B viruses to evaluate the role of HGBV-C in ALD. Serum samples were obtained from 68 patients with ALD and 40 nonalcoholic patients with chronic type C liver disease. HGBV-C RNA was detected in only 3 of 68 (4.4%) patients with ALD, in 2 of 27 patients with hepatic fibrosis, and in 1 of 5 patients with chronic hepatitis. There was no HGBV-C RNA in sera from patients with fatty liver, alcoholic hepatitis, or cirrhosis. Serum levels of AST, ALT, and gamma-glutamyltranspeptidase in alcoholic patients with, as well as without, HGBV-C RNA decreased to normal levels after abstinence. In addition, an inflammatory change was not observed in liver biopsy specimens obtained from two HGBV-C-positive patients with alcoholic hepatic fibrosis. Our results clearly suggest that the prevalence of HGBV-C infection in patients with ALD is rare and that HGBV-C may not play an important role in the development of liver disease in alcoholics.

Alcohol Drinking↗
PubMed1997

Synthesis of 6-aminouracils and pyrrolo[2,3-d]pyrimidine-2,4-diones and their inhibitory effect on thymidine phosphorylase.

Inhibitors of thymidine phosphorylase (dThdPase) are expected to suppress the growth and metastasis of tumor cells by inhibition of angiogenesis and were designed by utilizing the three dimensional structure of the enzyme. 5-Substituted 6-aminouracils (5) and 7-substituted pyrrolo[2,3-d]pyrimidine-2,4-diones (6) were synthesized and tested for inhibition of human placenta thymidine phosphorylase. 5-Bromo-6-aminouracil (5d), 5-cyano-6-[3-(methylamino)propyl]-uracil (5e), and 7-(2-aminoethyl)-pyrrolo[2,3-d]pyrimidine-2,4-dione (6c) inhibited dThdPase with IC50s of 7.6, 3.8 and 44.0 microM, respectively.

Antimetabolites, Antineoplastic↗
PubMed1996

Inhibition of the Met-enkephalin-induced K+ current in B-cluster neurons of Aplysia by nitric oxide donor.

The effects of sodium nitroprusside (SNP), a nitric oxide (NO) donor, on a methionine-enkephalin (Met-E)-induced K+ current recorded from B-cluster neurons in Aplysia cerebral ganglion were investigated with voltage-clamp and pressure ejection techniques. Bath-applied SNP (10-25 microM) reduced the Met-E-induced K+ current in the neurons without affecting the resting membrane conductance and holding current. The inhibitory effects of SNP were reversible. Pretreatment with methylene blue (10 microM), a non-specific inhibitor of guanylate cyclase, and hemoglobin (50 microM), a NO scavenger, decreased the SNP-induced inhibition of the Met-E-induced current. Intracellular injection of 1 mM guanosine 3',5'-cyclic monophosphate (cGMP) or bath-applied 3-isobutyl-1-methylxanthine (IBMX; 50 microM), a nonspecific phosphodiesterase inhibitor, inhibited the Met-E-induced current. Furthermore, 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1 microM), a more specific inhibitor of NO-stimulated guanylate cyclase, decreased the SNP-induced inhibition of the Met-E-induced current. These results suggest that SNP induces suppression of the Met-E-induced K+ current recorded from B-cluster neurons of Aplysia cerebral ganglion via stimulation of cGMP formation.

Animals↗
PubMed1996

Amyloid beta proteins reduce the GABA-induced Cl- current in identified Aplysia neurons.

The amyloid beta protein (A beta P) is the major component of the amyloid deposition which characterizes Alzheimer's disease. Effects of extracellularly applied A beta P on the gamma-aminobutyric acid (GABA)-induced Cl- current recorded from identified neurons (R9 and R12) of Aplysia kurodai were investigated with conventional voltage-clamp and pressure ejection techniques. Focal application of 100 nM A beta P (1-40) reduced the GABA-induced hyperpolarization at resting membrane potential and the GABA-induced Cl- current in the neurons held at -50 mV. Bath-applied 100 nM A beta P fragments (1-40) and (25-35) but not A beta P (1-16) inhibited the GABA-induced Cl- current as well as muscimol-induced Cl- currents in the neurons without affecting the resting membrane conductance or holding current. These results suggest that A beta P may increase neuronal excitability by inhibiting GABA-induced Cl- current in the neurons of mammalian central nervous system.

Amyloid beta-Peptides↗