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Biomedical subjects

M Oda

Publications and source records attributed to M Oda.

At least 91 records · Page 5Linked to original sources

Effects of constituents from the bark of Magnolia obovata on nitric oxide production in lipopolysaccharide-activated macrophages.

The methanolic extract from a Japanese herbal medicine, the bark of Magnolia obovata, was found to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-activated macrophages. By bioassay-guided separation, three neolignans (magnolol, honokiol, obovatol) and three sesquiterpenes (alpha-eudesmol, beta-eudesmol, gamma-eudesmol) were obtained as active constituents. A trineolignan (magnolianin), a phenylpropanoid glycoside (syringin), lignan glycosides (liriodendrin, (+)-syringaresinol 4'-O-beta-D-glucopyranoside) and a sesquiterpene (caryophyllene oxide) did not show any activity. On the other hand, sesquiterpene-neolignans (eudesmagnolol, clovanemagnolol, caryolanemagnolol, eudeshonokiol A, eudesobovatol A) showed the strong cytotoxic effects. Active constituents (magnolol, honokiol, obovatol) showed weak inhibition for inducible NO synthase (iNOS) enzyme activity, but potent inhibition of iNOS induction and activation of nuclear factor-kappaB.

Animals↗

[A case of recurrent ischemic attacks: consecutive diffusion-weighted magnetic resonance imaging].

A 61-year-old man with recurrent ischemic attacks was examined by diffusion-weighted MRI (DWI). He had reversible right hemiparesis and dysarthria five times during admission. DWI was obtained on the first two attacks, the last attack and four days after the last attack. The first two attacks were clinically diagnosed as transient ischemic attack (TIA), and the last attack was cerebral infarction with symptoms persistent for one week with Babinski's sign. In the first and last images the apparent diffusion coefficient (ADC) declined to approximately 80% of the corresponding area. We conclude that different images showed TIA with ADC declining, TIA without ADC declining, the hyperacute phase of cerebral infarction before ADC declining, and cerebral infarction after ADC declining. Consecutive DWIs were helpful to understand the character of recurrent ischemic attacks.

Brain↗

Clinical analysis and prognostic study of ossified ligamentum flavum of the thoracic spine.

OBJECT: A variety of factors may affect surgery-related outcome in patients with ossification of the ligamentum flavum (OLF) of the thoracic spine. The aim of this study was to determine these factors on the basis of preoperative clinical and radiological findings. METHODS: The authors treated 31 cases of symptomatic thoracic OLF between 1988 and 1999. The following factors were retrospectively studied: patient age, sex, morbidity level, initial symptoms, chief complaint, duration of symptoms, patellar reflex, Achilles reflex, computerized tomography (CT) finding, presence of intramedullary change determined by magnetic resonance imaging, coexistent spinal lesions, preoperative grade, and postoperative grade. A decompressive laminectomy was performed in all cases. In 29 patients (94%) improved symptoms were demonstrated postoperatively. In terms of functional prognosis, the preoperative duration of symptoms was significantly shorter in the group of patients with excellent outcomes than in those with fair outcomes (p < 0.05). No significant difference was observed in the correlation between other factors. To evaluate the degree of preoperative thoracic stenosis and the severity/extent of OLF-induced spinal compression, we used an original OLF CT scoring system. A score of excellent on the CT scale tended to indicate an excellent prognosis (p < 0.01). CONCLUSIONS: Thoracic OLF frequently develops in the lower-thoracic spine in middle-aged men, and it is complicated by various spinal lesions in many cases. Early diagnosis and treatment are important for understanding the clinical symptoms and imaging diagnosis because the present findings suggest that a delay in diagnosis and treatment correlates with the functional prognosis postoperatively.

Adult↗

[Prefabrication of vascularized bone flap using bone morphogenetic protein (BMP)].

The purpose of this study was to produce newly vascularized bone, and to form the bone into the desired shape. Silicone molds given the shape of a cylinder were used to deliver collagen sheets impregnated with or without rhBMP-2. The superficial inferior epigastric neurovascular bundle in a Wistar rat was identified and sandwiched between the silicone molds. The molds containing collagen sheets impregnated with 10 micrograms of rhBMP-2 were used for the experimental purpose, and those without rhBMP-2 were used as a control. In some of the experimental molds, the neurovascular bundle was ligated at both proximal and distal sites of the molds. After 2 and 4 weeks operation, bone formation was detected macroscopically, radiologically, and histologically. As a result, newly formed bone was observed in all experimental sites without the ligation, and the shape of the bone was exactly the same shape as the silicone mold. Newly formed bone was supplied by the superficial inferior epigastric artery, whereas newly formed bone was not observed in the control and the ligated flaps. Newly vascularized and shaped bone was created by applying an osteoinductive factor to a neurovascular bundle. This study demonstrates that this experimental model could be a therapeutically potential approach for effective bone reconstruction.

Animals↗

Biological characteristics of carcinomatosa pleuritis in orthotopic model systems using immune-deficient rats.

We assessed the association of vascular endothelial growth factor (VEGF) on the formation of carcinomatosa pleuritis in orthotopic model systems. Immune-deficient rats were inoculated with PC-14 cells into i) a subpleural space of the parietal pleura after pneumonectomy or ii) into the thoracic cavity directly. The rats bearing tumor cells were randomly separated into two groups: non-treatment and treatment with anti-VEGF neutralizing antibody groups. At the time of the autopsy, all rats developed gross pleural dissemination with/without malignant effusions. In the first model, despite no significant difference in the mean volume of the subpleural tumors between the groups, the degree of dissemination was suppressed in the treatment group with less tumor vasculature and with reduced expression of autocrine motility factor receptor (AMFR) in tumor cells. In the second model, although the inhibitory effect on dissemination was not clear, the formation of pleural effusion was inhibited in the treatment group. In addition to the ability of vascular permeability, the results demonstrated here showed the possible association of VEGF with the development of pleural dissemination/metastasis in the context of blood/lymphatic routes and cancer cell motility affected by AMFR.

Adenocarcinoma↗

[Carinal resection for bronchogenic carcinoma].

The purpose of this study was to evaluate the results of carinal resection for bronchogenic carcinoma in our institute. From 1981 to 1999, 24 carinal resection were performed for squamous cell carcinoma (n = 19), adenoid cystic carcinoma (n = 2), small cell carcinoma (n = 1), adenocarcinoma (n = 1), and mucoepidermoid carcinoma (n = 1). Nineteen underwent sleeve pneumonectomy, 2 had carinal resection without lung resection, 2 had carinal resection with right middle and lower lobectomy, and 1 had wedge pneumonectomy. In the patients with sleeve or wedge pneumonectomy, there were 5 operative death and 3 patients had survived for more than 3 years. Two patients with low-grade malignant tumors underwent carinal resection without lung resection and survived more than 10 years. We believe that limited carinal resection for low-grade malignant tumors are safe and valuable procedure. Careful selection of patients with sleeve or wedge pneumonectomy is mandatory.

Adult↗

[Cerebral infarction presenting pure motor monoparesis: diagnosis by diffusion-weighted MR imaging].

We studied 10 patients with acute ischemic cerebrovascular disorders presenting paralysis confined to one limb, unaccompanied by sensory signs(pure motor monoparesis, PMM) on diffusion-weighted MR imaging(DWI). DWI revealed fresh ischemic lesions in all patients, except for 2 cases of transient ischemic attack. On DWI, acute infarction in multiple lesions was identified, and small superficial lesions were clearly described. Superficial lesions were seen in 4 patients, and deep lesions were also seen in 4 patients. DWI is useful for lesion analysis in cerebral infarction with PMM.

Aged↗

[A case of inflammatory myopathy worsened by miscarriage with autoimmune disorder-associated disease].

The patient was 42-year-old woman who had exhibited elevated levels of serum creatine kinase(CK) and intermittent weakness of proximal muscles since her thirties. She had a history of palmoplantar pustulosis, Mondor's disease and recurrent miscarriages. Basedow's disease, which had been treated with antithyroid drugs since 37 years of age, recurred during the fourth pregnancy. After the pregnancy was terminated in the sixth week, weakness and grasp pain in the proximal muscles developed. The biopsy of biceps brachii muscle showed necrosis and reconstruction of muscle fibers with equivocal inflammatory cells, which was compatible with the findings for inflammatory myopathy such as polymyositis(PM). She was treated with prednisolone and the weakness and grasp pain in the proximal muscles were resolved. PM beginning during a woman's reproductive period is rare, and few studies have examined the association between PM and pregnancy. In this case, pregnancy and her past diseases were considered to be linked to an autoimmune abnormality that might have contributed to the inflammatory myopathy.

Abortion, Habitual↗

Modification of guide wire for 22-gauge safe guide.

Safe guide is a central venous catheterization kit that serves as both pilot needle and introducer. With a single puncture, a guide wire can be introduced by inserting it through the side port of the 22-gauge needle. The advantage is that this needle can be placed within a blood vessel using no more force than is required to insert a pilot needle. However, the 0.018-inch guide wire is vulnerable to kinks and locking. Because the tip has been shaped into a sharp J-shaped angle, it can kink at the puncture site, and locking sometimes occurs when the guide wire is passed through the side port of the needle, or when the dilator is introduced. In order to resolve these issues, we modified the device by making an experimental guide wire with a gentler angle. In addition, we fortified the body of the wire without altering its thickness. We then investigated the effectiveness of our modifications. The subjects of the study were 120 patients, who required central venous catheterization. They were divided into 2 groups. The original J-type guide wire was used in one group (Group A: n = 60) and the modified guide wire in the other group (Group B: n = 60). Catheters were introduced by right internal jugular vein puncture. We observed the following: 1) incidence of back-flow appearing at withdrawal of the needle without back-flow during advancement, 2) incidence of kinking or locking of the guide wire when it was passed through the side port, 3) incidence of kinking of the guide wire at the puncture site when introducing the dilator, and 4) complications. The results were as follows: 1) back-flow appeared upon withdrawal in 3.4% of both groups; 2) kinking and locking occurred when passing the guide wire through the side port of the Safe guide needle in 16.7% of Group A and 1.7% of Group B; 3) kinking of the guide wire occurred when introducing the dilator in 5 % of Group A in contrast to 0% in Group B; 4) the only complication caused by the passing of the guide wire was accidental puncture of the common carotid artery, which occurred in 1.7% of both groups. No problems with the guide wire were noted in either group. The use of our modified guide wire decreased the incidence of kinking and locking of the guide wire when passing it through the side port. In addition, no guide wire kinking at the puncture site occurred when introducing the dilator. Issues associated with the original J-type guide wire were resolved by 1) changing the guide wire tip to a gentler angle, and 2) fortifying the guide wire by altering its composition.

Catheterization, Central Venous↗

Release of plasminogen activator inhibitor-1 from human astrocytes is regulated by intracellular ceramide.

The present study underscores a regulatory role of intracellular ceramide in astrocytes for the release of an extracellular serine protease, tissue-type plasminogen activator (t-PA), and its inhibitor, plasminogen activator inhibitor-1 (PAI-1). Treatment of cultured human astrocytes with N-acetylsphingosine, a cell-permeable short-chain ceramide analogue or daunorubicin that could increase intracellular ceramide via activation of ceramide synthase or sphingomyelin hydrolysis increased the release of t-PA and conversely decreased the PAI-1 release. Interestingly, treatment of the astrocytes with tumor necrosis factor (TNF)-alpha also increased the intracellular ceramide levels but caused the elevation of PAI-1 release without altering the t-PA release. These data suggest that the generation of ceramide in astrocytes is linked at least with the regulation of PAI-1 release. We also demonstrate that the suppression of PAI-1 release with daunorubicin accelerates the cell death of neuronally differentiated PC12 cells and suggest an antiapoptotic role of PAI-1 in the nervous system.

Animals↗

Surgical management of early stage central (hilar) and peripheral nonsmall cell lung carcinoma.

BACKGROUND: To the authors' knowledge, the definitions of early lung carcinoma used in Japan are not yet approved internationally. In the current study the diagnostic methods, pathology, and results of the surgical treatment of early hilar and peripheral nonsmall cell lung carcinoma cases defined by Japanese criteria are presented. METHODS: Between 1977 and 1998, 43 patients with early hilar lung carcinoma were encountered. These patients constituted 14.5% of 200 hilar lung carcinoma patients who underwent resection during the same period. Between 1973 and 1998, there were 174 early peripheral lung carcinomas, which comprised 14.8% of 1173 peripheral lung carcinoma patients who underwent resection during the same period. RESULTS: The 5-year and 10-year survival rates of the early hilar lung carcinoma were 100% and 96.9%, respectively. The majority of the patients underwent bronchoplastic surgery, such as sleeve lobectomy and parenchymal-sparing surgery including seven sleeve segmentectomies and two second carinal resections. The effectiveness of the parenchymal-sparing resections was assessed by the conventional pulmonary function test as well as perfusion and ventilation scanning. There were 174 cases of peripheral early lung carcinoma among the 218 cases of peripheral lung carcinoma with tumor dimensions of < or = 2 cm. The cell types were 142 (81.6%) cases of adenocarcinoma, 18 (10.3%) cases of squamous cell carcinoma, and 14 (8%) cases of other cell types. These 174 patients comprised 14.8% of 1173 patients with peripheral nonsmall cell lung carcinoma who underwent surgery during the same period. The 5-year and 10-year survival rates for adenocarcinoma were 89.6% and 86.8%, respectively. The 5-year and 10-year survival rates for other cell types were both 71.8%. The overall 5-year and 10-year survival rates were 86.8% and 84.6%, respectively. CONCLUSIONS: Early lung carcinoma in both the hilar and peripheral regions, is curable if it is properly diagnosed and treated.

Aged↗

The biochemical mode of inhibition of DNA polymerase beta by alpha-rubromycin.

Quinone antibiotics, alpha- and beta-rubromycin, were originally found as inhibitors of retroviral reverse transcriptase. We investigated the effects of these agents on DNA metabolic enzymes including DNA and RNA polymerases as retroviral reverse transcriptase is a kind of the polymerase. As expected, we found that alpha- and beta-rubromycin strongly inhibited not only the retroviral reverse transcriptase activity, but the activities of the mammalian DNA polymerases, telomerase and terminal deoxynucleotidyl transferase in vitro. These agents should therefore be classified as DNA polymerase inhibitors. The Ki values of alpha-rubromycin against nucleotide substrate were 0.66 and 0.17 microM for DNA polymerase alpha and beta (pol. alpha and beta), respectively, and those of beta-rubromycin was 2.40 and 10.5 microM, respectively. Alpha-rubromycin strongly inhibited the pol. beta activity, and showed the strongest pol. beta inhibitory effect reported to date. At least on pol. beta, alpha-rubromycin was suggested to bind to the active region competing with the nucleotide substrate, and subsequently inhibit the catalytic activity. alpha-Rubromycin directly competed with the nucleotide substrate, and indirectly but simultaneously and non-competitively disturbed the template-DNA interaction with pol. beta.

Animals↗

Synthesis and characterization of water-soluble silver(I) complexes with L-histidine (H2his) and (S)-(-)-2-pyrrolidone-5-carboxylic acid (H2pyrrld) showing a wide spectrum of effective antibacterial and antifungal activities. Crystal structures of chiral helical polymers [Ag(Hhis)]n and ([Ag(Hpyrrld)]2)n in the solid state.

Two water-soluble, silver(I) complexes showing a wide spectrum of effective antibacterial and antifungal activities, i.e., ([Ag(Hhis)].0.2EtOH)2 (1; H2his = L-histidine) and [Ag(Hpyrrld)]2 (3; H2pyrrld = (S)-(-)-2-pyrrolidone-5-carboxylic acid) were prepared. In aqueous solution 1 and 3 were present as dimers, whereas in the solid state they were polymers. Crystallization of 1 by slow evaporation and/or vapor diffusion gave water-insoluble crystals of [Ag(Hhis)]n (2) showing modest antimicrobial activities. The complex 1 in the solid state is a polymer formed by intermolecular hydrogen-bonding interactions between dimeric [Ag(Hhis)]2 cores, while 2 is a different polymer without a core complex. X-ray crystallography revealed that 2 was a left-handed helical polymer consisting of a bent, 2-coordinate silver(I) atom bonding to the Namino atom of one Hhis- ligand and the N pi atom of a different Hhis- ligand. Of particular note is the fact that Ocarboxyl atoms do not participate in the coordination. X-ray crystallography also revealed that 3 was a left-handed helical polymer formed by self-assembly of dimeric [Ag(Hpyrrld)]2 cores with an intramolecular metal(I)-metal(I) interaction (Ag-Ag distance, 2.9022(7) A). The FT-IR and the solid-state 13C and 15N NMR spectra showed that the dimeric core of 1 was formed through Ag-N bonds, while that of 3 was formed through Ag-O bonds. The molecular ions of 1 and 3 were detected by the positive-ion electrospray ionization (ESI) mass spectrometry. For 1-3, characterization by elemental analysis, TG/DTA, FT-IR, and variable-temperature solid-state 13C NMR and room-temperature 15N NMR measurements was performed, and for 1 and 3, that by solution molecular weight measurements and solution (109Ag, 1H, and 13C) NMR spectroscopies was also carried out. The antibacterial and antifungal activities of 1 and 3 were remarkable and comparable to those of the previous silver(I)-N-heterocycle complexes.

Anti-Bacterial Agents↗

Inhibition of human telomerase by rubromycins: implication of spiroketal system of the compounds as an active moiety.

We found that a group of rubromycins and their analogues, a class of quinone antibiotics that possesses benzofuran and benzodipyran rings to form a spiroketal system, strongly inhibited human telomerase as assessed with a modified telomeric repeat amplification protocol. beta- and gamma-Rubromycins and purpuromycin appeared to be the most potent telomerase inhibitors, with 50% inhibitory concentrations (IC(50)) of about 3 microM, and griseorhodins A and C also showed comparable potencies for the inhibition (IC(50) = 6-12 microM). In contrast, opening of the spiroketal system of beta-rubromycin, giving rise to alpha-rubromycin, substantially decreased its inhibitory potency toward telomerase (IC(50) > 200 microM), indicating the essential role of the spiroketal system in telomerase inhibition. A kinetic study of the inhibition by beta-rubromycin revealed a competitive interaction with respect to the telomerase substrate primer, with a K(i) of 0.74 microM, whereas a mixed type inhibition was observed with respect to the nucleotide substrate. beta-Rubromycin was also potent in inhibiting retroviral reverse transcriptases but had virtually no effect on other DNA/RNA-modifying enzymes including DNA and RNA polymerases, deoxyribonuclease, and topoisomerase. Although beta-rubromycin showed nonspecific cytotoxicities, reducing proliferation of cancer cells (IC(50) approximately 20 microM), we conclude that beta-rubromycin appears to be a lead structure for the development of more potent and selective inhibitors of human telomerase.

Anti-Bacterial Agents↗

A post-traumatic ligamentum flavum progressive hematoma: a case report.

STUDY DESIGN: A case report. OBJECTIVES: To understand a rare case of ligamentum flavum progressive hematoma. SUMMARY OF BACKGROUND DATA: Previously there were only two reports about ligamentum flavum hematoma. METHODS: A patient was surgically treated for ligamentum flavum hematoma causing progressive L5 radiculopathy. Clinical and neuroradiologic features were reported, and the literature was reviewed. RESULTS: The etiology of this case could not be defined except by minor back injury. In spite of conservative therapy, the symptoms were progressive for 7 months. Magnetic resonance imaging demonstrated the epidural mass lesion at L4-L5 that was continuous with the ligamentum flavum. The mass was hypointense in T1-weighted images and central hyperintense and marginal hypointense in T2-weighted images. The margin was well enhanced by Gd-DTPA administration. After removal of the mass lesion, the patient's symptoms completely resolved. Before surgery, accurate diagnosis was difficult even based on magnetic resonance imaging and was achieved after histologic examinations. CONCLUSIONS: Surgery could be a choice of the treatment modality to resolve symptoms in ligamentum flavum hematoma.

Hematoma↗

Autonomic failure in ALS with a novel SOD1 gene mutation.

The authors report a patient with ALS and a novel SOD1 gene mutation who was in the totally locked-in state and developed autonomic failure followed by sudden cardiac arrest. A neuropathologic study showed widespread multisystem degeneration, including involvement of the autonomic nuclei in the medulla and spinal cord. SOD1 gene analysis detected a missense mutation of V118L in exon 4. These findings show notable phenotypic heterogeneity for SOD1-associated ALS.

Adult↗

Vicinal dithiol-binding agent, phenylarsine oxide, inhibits inducible nitric-oxide synthase gene expression at a step of nuclear factor-kappaB DNA binding in hepatocytes.

Inflammatory cytokine interleukin 1beta induces inducible nitric-oxide synthase (iNOS) mRNA and its protein, which are followed by increasing the production of nitric oxide, in primary cultures of rat hepatocytes. Nuclear factor-kappaB (NF-kappaB), an important transcription factor for iNOS gene expression, is also activated and translocated to the nucleus. In the present study, we found that vicinal dithiol-binding agent, phenylarsine oxide (PAO), inhibited the induction of iNOS protein and mRNA as well as the release of nitrite (nitric oxide metabolite) into the culture medium. Simultaneous addition of a vicinal dithiol compound, 2, 3-dimercaptopropanol, with PAO completely abolished these inhibitions. PAO could not prevent either degradation of an inhibitory protein, IkappaB, of NF-kappaB or translocation of NF-kappaB to the nucleus. However, electrophoretic mobility shift assay demonstrated that PAO decreased the interaction between NF-kappaB and its binding consensus oligonucleotide. Transfection experiments with iNOS promoter-luciferase construct revealed that PAO inhibited NF-kappaB binding to DNA. These results indicate that PAO inhibits iNOS gene expression at a step of NF-kappaB binding to DNA by modifying its vicinal dithiol moiety, which may play a crucial role for the iNOS regulation in hepatocytes.

Animals↗