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Biomedical subjects

M Okamoto

Publications and source records attributed to M Okamoto.

At least 289 records · Page 16Linked to original sources
PubMed1999

Ultrasonographic evidence of association of polyps and stones with gallbladder cancer.

OBJECTIVE: The purpose of this study was to evaluate the level of gallbladder cancer risk associated with polyps and stones of the gallbladder by ultrasound examinations. METHODS: We investigated abdominal ultrasonographic findings for gallstones and polyps of the gallbladder and the relationship of these findings to malignancy in 194,767 asymptomatic participants in health screening examinations. RESULTS: Gallstones were detected in 7,985 participants (4.1%), at a prevalence of 5.3% in male and 4.5% in female participants. The prevalence was highest in the participants' seventh decade, followed by the sixth and the fifth decades, in both male and female participants. Polyps were found in 10,926 (5.6%), at a prevalence of 6.9% in the male and 4.5% in the female participants. In the male participants, prevalence was highest in the fourth decade, followed by the third and the fifth decades, whereas in the female participants it was highest in the fifth decade, followed by the fourth and third. High prevalence of polyps > or = 10 mm in diameter was found in the fifth to seventh decades in both sexes. Nineteen participants (0.01%) were diagnosed as having gallbladder cancer, and many of them were in the sixth or seventh decade in both sexes. Patients with stones showed a higher prevalence of gallbladder cancer. This difference was shown to be statistically significant by age-adjusted analysis (p < 0.01). The age distribution of the participants with polyps > or = 10 mm in diameter was correlated with that of patients diagnosed with gallbladder cancer. Furthermore, polyp incidence was significantly related to cancer by statistical analysis (p < 0.01). CONCLUSION: These results suggest an association between gallstone or polyp of the gallbladder and increased risk of malignancy, implying that an etiological association may also exist.

Adult↗
PubMed1999

Inhibition of human immunodeficiency virus type 1 replication in acutely and chronically infected cells by EM2487, a novel substance produced by a Streptomyces species.

In a search for effective HIV-1 transcription inhibitors, we have evaluated more than 75,000 compounds for their inhibitory effects on Tat-induced human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR)-driven reporter gene expression and found that EM2487, a novel small-molecule substance produced by a Streptomyces species, is a potent and selective inhibitor of HIV-1 replication in both acutely and chronically infected cells. Its 50% effective concentration for acute HIV-1 infection was 0.27 microM in peripheral blood mononuclear cells (PBMCs), while the 50% cytotoxic concentration for mock-infected PBMCs was 13.3 microM. EM2487 proved inhibitory to a variety of HIV-1 strains and HIV-2 in acutely infected T-cell lines (MOLT-4 and MT-4). The compound could suppress tumor necrosis factor alpha (TNF-alpha)-induced HIV-1 production in latently infected cells (OM-10.1 and ACH-2) as well as constitutive viral production in chronically infected cells (MOLT-4/III(B) and U937/III(B)) without showing any cytotoxicity. EM2487 did not affect early events of the HIV-1 replication cycle, as determined by proviral DNA synthesis in acutely infected MOLT-4 cells. In contrast, the compound selectively prevented viral mRNA synthesis in OM-10.1 cells, suggesting that HIV-1 inhibition occurs at the transcriptional level. Furthermore, EM2487 did not inhibit TNF-alpha-induced HIV-1 LTR-driven reporter gene expression but did inhibit that induced by Tat, irrespective of the presence or absence of the nuclear factor kappaB binding sites in the LTR. These results suggest that the mechanism of action is attributable in part to the inhibition of Tat function.

Anti-HIV Agents↗
PubMed1999

Inhibition of human immunodeficiency virus type 1 replication by combination of transcription inhibitor K-12 and other antiretroviral agents in acutely and chronically infected cells.

8-Difluoromethoxy-1-ethyl-6-fluoro-1,4-dihydro-7-[4-(2-methoxyp hen yl)-1- piperazinyl]-4-oxoquinoline-3-carboxylic acid (K-12) has recently been identified as a potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) transcription. In this study, we examined several combinations of K-12 and other antiretroviral agents for their inhibitory effects on HIV-1 replication in acutely and chronically infected cell cultures. Combinations of K-12 and a reverse transcriptase (RT) inhibitor, either zidovudine, lamivudine, or nevirapine, synergistically inhibited HIV-1 replication in acutely infected MT-4 cells. The combination of K-12 and the protease inhibitor nelfinavir (NFV) also synergistically inhibited HIV-1, whereas the synergism of this combination was weaker than that of the combinations with the RT inhibitors. K-12 did not enhance the cytotoxicities of RT and protease inhibitors. Synergism of the combinations was also observed in acutely infected peripheral blood mononuclear cells. The combination of K-12 and cepharanthine, a nuclear factor kappa B inhibitor, synergistically inhibited HIV-1 production in tumor necrosis factor alpha-stimulated U1 cells, a promonocytic cell line chronically infected with the virus. In contrast, additive inhibition was observed for the combination of K-12 and NFV. These results indicate that the combinations of K-12 and clinically available antiretroviral agents may have potential as chemotherapeutic modalities for the treatment of HIV-1 infection.

Alkaloids↗
PubMed1999

Nephrotic mice (ICGN strain): a model of diffuse mesangial sclerosis in infantile nephrotic syndrome.

The ICGN mouse strain is a unique model for naturally occurring nephrotic syndrome. In the present study, we examined the onset of the clinical manifestation of nephrotic syndrome and determined the sequence of intraglomerular events associated with progression of nephrotic conditions. Laboratory analysis revealed that homozygous (nep/nep) mice showed urinary albumin excretion during the suckling stage, rapidly leading to hypoalbuminemia accompanied by body growth failure. Renal pathology demonstrated that an initial intraglomerular event in the nephrotic mice was observed 3 weeks after birth in the form of mesangiolytic lesions, characterized by microaneurysm, platelet accumulation and capillary ballooning. In 6-week-old homozygous mice, mesangial sclerosis, characterized by mesangial expansion and glomerular hypertrophy, was observed in a diffuse fashion. Immunohistochemistry revealed that the glomerular cells in the 3-week-old homozygous suckling mice were positive for alpha-smooth muscle actin, suggesting a phenotypic change in the mesangial cells. Mesangial expansion, confirmed by the over-deposition of type I collagen, was evident until 6 weeks after weaning, while it was of interest that fibrogenic cytokines such as platelet-derived growth factor and transforming growth factor-beta were not detected in the sclerotic glomeruli throughout the observations. Furthermore, the nephrotic features were shown to be resistant to steroid therapy with a high dose of prednisolone. Our results suggest that diffuse mesangial sclerosis, a hereditary glomerular disease, may be genetically generated through early myofibroblast formation, which occurs and develops probably independently of up-regulation of these fibrogenic cytokines. In conclusion, the homozygous nephrotic mouse (ICGN strain) is believed to be a good model for investigating not only nephrotic conditions but also cellular and molecular pathogenesis of diffuse mesangial sclerosis in steroid-resistant infantile nephrotic syndrome.

Albuminuria↗
PubMed1999

Inhibition of human immunodeficiency virus replication by RD6-Y664, a novel benzylhydroxylamine derivative.

We have examined novel benzylhydroxylamine derivatives for their inhibitory effects on the replication of human immunodeficiency virus (HIV) in cell cultures. Among the series, O-(2-chloro-6-fluorobenzyl)hydroxylamine (RD6-Y664) was found to be the most potent inhibitor of HIV-1. The EC50 for HIV-1 strain IIIB was 1.6 micrograms/ml with a selectivity index greater than 38 in MT-4 cells. It also inhibited the replication of other HIV strains including a non-nucleoside reverse transcriptase (RT) inhibitor-resistant mutant, a nucleoside RT inhibitor-resistant mutant and HIV-2, in acutely infected cells. However, the compound did not affect HIV-1 production in chronically infected cells. A time-of-addition experiment and detection of proviral DNA synthesis suggested that RD6-Y664 targeted an early step of the viral replication cycle, presumably a process prior to reverse transcription. In fact, an assay for HIV-1 RT revealed that the compound did not suppress enzyme activity. Furthermore, RD6-Y664 did not show any inhibition of gp120-CD4 interaction, or binding of anti-CXCR4 antibody to CXCR4.

Anti-HIV Agents↗
PubMed1999

Characterization of human immunodeficiency virus type 1 strains resistant to the non-nucleoside reverse transcriptase inhibitor RD4-2217.

The non-nucleoside reverse transcriptase (RT) inhibitor RD4-2217 is a thiadiazole derivative that has proved to be a highly potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) replication in vitro. In this study we examined genotypic and phenotypic characteristics of RD4-2217-resistant mutants that have been obtained by serial passage of HIV-1 in MT-4 cells in the presence of increasing concentrations (0.05, 0.25, 1 and 10 microM) of the compound. The strains obtained, III(B/2217RE/0.05) and III(B/2217RE/0.25,) were two- and 15-fold resistant to RD4-2217, respectively, whereas III(B/2217RE/1) and III(B/2217RE/10) displayed 161- and >238-fold resistance, respectively. Both III(B/2217RE/1) and III(B/2217RE/10) had two amino acid substitutions, V1891 and T2401, in the RT. Furthermore, RD4-2217 did not inhibit the replication of an HIV-1 molecular clone, which had the same mutation, at concentrations up to 10 microM, indicating that the V1891 plus T2401 mutation confers high-level resistance to RD4-2217. Interestingly, the replicability of III(B2217RE/1) and III(B/2217RE/10) appeared to be lower than that of wildtype III(B) in MT-4 cells, suggesting that the V1891 plus T2401 mutation may impair the enzymatic activity of HIV-1 RT.

Anti-HIV Agents↗
PubMed1999

Transcatheter coil embolization of large-size patent ductus arteriosus in adult patients: usefulness and problems.

Transcatheter coil embolization of the patent ductus arteriosus (PDA) has been frequently used in children, especially for small lesions. It was attempted in 3 adults using Cook detachable coils. For 2 of the patients, relatively old age and heart failure were the reasons for choosing coil embolization of the PDA. In the remaining patient, who had Wolff-Parkinson-White syndrome, coil embolization was performed after radiofrequency catheter ablation of Kent's bundle. Their respective minimal PDA diameters were 5.0 mm, 4.5 mm and 4.0 mm measured by transesophageal echocardiography. Two coils were placed in 2 patients and 1 coil in the remaining patient. After the procedures, the size of the left ventricle decreased and heart failure was improved in 2 patients, although all 3 patients had a residual shunt, which caused hemolytic anemia in 2 patients. Repeat coil-embolization procedures resulted in complete occlusion and the hemolysis disappeared in these patients. In adult patients who have heart failure due to large PDA, coil embolization with detachable coils, even if residual shunt persists, is useful for improvement of the heart failure. In cases of hemolysis related to residual shunt, a second coil-embolization procedure can improve it completely.

Adult↗
PubMed1999

A novel Na+ and Ca2+ channel blocker, T-477, prevents brain edema following microsphere-induced permanent occlusion of cerebral arterioles in rats.

One of the most common acute complications of stroke is brain edema. Treatment of edema is recommended when the condition of the patients is deteriorating. The present study was undertaken to evaluate the effect of T-477 [(R)-(+)-2-(4-chlorophenyl)-2,3-dihydro-4-diethyl aminoacetyl-4H-1,4-benzorthiazine hydrochloride], a novel neuronal Na+ and Ca2+ channel blocker, on brain edema in rats. Cerebral ischemia was induced by intra-arterial infusion of 1000 microspheres into the forebrain of freely moving rats, resulting in brain edema. T-477 was intravenously infused continuously for 24 h or twice for 3 h with a 3-h interval between infusions immediately after microsphere injection. T-477 dose-dependently inhibited the increase in brain water content by both infusion procedures; the inhibition was statistically significant at doses of 25 mg/kg per 24 h and 14 mg/kg per 9 h. Additionally, infusion of T-477 at a dose of 14 mg/kg per 9 h significantly inhibited the decrease in K content and the increase in Ca content of the forebrain. In conclusion, T-477 prevents brain edema following microsphere-induced cerebral embolism in rats.

Animals↗
PubMed1999

Production of germfree mice by embryo transfer.

We applied the embryo transfer technique to germfree (GF) mouse production. Embryos harvested from superovulated mice were transferred aseptically, in a sterile environment, to the uterus of GF recipient females which had been mated with vasectomized GF males. One of the recipients became pregnant and delivered offspring. Sterility tests confirmed that the vasectomized males, newborns, recipient female mice, embryo-containing culture media, and the inside of the vinyl film isolator were germfree. These results suggest that the embryo transfer technique can be successfully applied to the production of GF mice.

Animals↗
PubMed1999

Reappraisal of potassium permanganate oxidation applied to Lowicryl K4M embedded tissues processed by high pressure freezing/freeze substitution, with special reference to differential staining of the zymogen granules of rat gastric chief cells.

The high pressure freezing/freeze substitution technique is known to yield a deep vitreous freezing of tissues. Combination of this technique with Lowicryl K4M embedding allows us histochemical studies of dynamic cellular processes with improved structural preservation. The disadvantage of Lowicryl K4M embedding is its poor electron density in electron microscopy. To address this problem, we examined the effects of KMnO4 oxidation applied to Lowicryl K4M embedded rat gastric glands processed by high pressure freezing. The KMnO4 oxidation-uranyl acetate-lead citrate sequence succeeded not only in contrast enhancement of cellular components, but also in differential staining of the zymogen granules of rat gastric chief cells. This technique could be applied to semi-thin sections of Lowicryl K4M embedded rat gastric glands. The KMnO4 oxidation-toluidine blue staining provided sufficient contrast with regard to the zymogen granules. Various experiments used in this study verified that the KMnO4 oxidation plays an essential role in the differential staining of the zymogen granules. Combined use of the KMnO4 oxidation with phospholipase A2-immunostaining demonstrated that gold labeling was localized to the zymogen granules without the loss of immunolabeling. Energy dispersive X-ray microanalysis revealed some manganese depositions on the zymogen granules. It is highly anticipated that the KMnO4 oxidation will become a useful tool for histochemical investigations combined with cryofixation/freeze substitution and low temperature embedding techniques.

Acrylic Resins↗
PubMed1999

Giant cell arteritis associated with rheumatoid arthritis monitored by magnetic resonance angiography.

A 57-year-old Japanese woman with well controlled rheumatoid arthritis visited our hospital with a severe bitemporal headache and marked fatigue. Based on the classification criteria by the American College of Rheumatology, she was diagnosed as having giant cell arteritis. Magnetic resonance (MR) angiography was performed, from which stenotic changes in the bilateral superficial temporal arteries were strongly suspected. Corticosteroid therapy was quickly started. The patient followed an uneventful course with no complications. Therapeutic effect was confirmed by MR angiographic findings obtained 4 weeks after the initiation of therapy.

Anti-Inflammatory Agents↗
PubMed1999

[A prospective study of introducing self-determined treatment policy for the patients with hypopharyngeal cancer].

A total of 57 patients with hypopharyngeal cancer were given an opportunity to select their treatment options after a thorough explanation of the tumor stage, treatment modalities, complications due to treatment, and prognosis. As a result, many patients selected chemoradiotherapy as the initial treatment. Two patients requested treatment at other institutes and were immediately transferred. A 91-year-old patient with T4N3M0 tumor declined treatment. The duration from the initial visit to the start of treatment course was prolonged because of the informed consent process. Patient rejection of salvage surgery following the failure of chemoradiotherapy increased. However, both the physician-patient relationship and physician-patient's family relationship in the uncured group did not deteriorate. No change in the 3-year crude survival rate by introducing self-determined treatment was observed at this time. It is ideal that the patient choice of treatment options is the one physician recommend. Meanwhile, physicians should consider ideal treatment options, which are most desirable for the patient. In conclusion, thorough informed consent provides positive clinical impact even with ominous hypopharyngeal cancer.

Aged↗
PubMed1999

Release and recharge of fluoride by restorative materials.

This study investigated the release and recharge of fluoride by restorative materials. Resin-modified glass ionomers (RGIs), polyacid-modified composite resins (PMCRs) and resin composite containing fluoride were used for comparison of fluoride release. Non-fluoride-releasing resin composite was used as a control. The amounts of fluoride release from RGIs and PMCRs remarkably increased in the citrate-phosphate acid buffer compared with distilled water. The amounts of fluoride recharged in RGIs increased with the concentration of NaF solution, but those of PMCRs exposed to all concentrations of NaF solutions were less than 1.5 ppm. Neither resin composite containing fluoride and non-fluoride-releasing resin composite gave any evidence of recharge. RGIs and PMCRs affected by acid buffer solution could not recharge much fluoride even if they were immersed in the 1000 ppmF NaF solution. The results suggested that the matrix of RGIs and PMCRs functioned as a reservoir of fluoride, but the functions were lost by acid attack.

Adsorption↗
PubMed1999

[Clinical study of radical retropubic prostatectomy for prostate cancer].

PURPOSE: To evaluate the results of radical retropubic prostatectomy in patients treated at a single institution. MATERIALS AND METHODS: Between April 1985 and July 1997, 76 patients with prostate cancer underwent radical retropubic prostatectomy, including 73 receiving pelvic lymphadenectomy. The median age and follow-up time were 68 years old and 44 months, respectively. The pathological stage was pT0 in 6 patients, pT2 in 29, pT3 in 39, pT4 in 2, and pN+ in 22. RESULTS: The surgical margin was positive in 10% of the pT2 patients and 61% of the pT3 patients. Twelve patients had recurrence. Recurrence was shown by biological failure in 4 patients and clinical failure in 8. The disease-free 5-year survival rates (Kaplan-Meier) were 100% in pT0 patients, 87% in pT2, 72% in pT3, 50% in pT4, 77% in pN-, 75% in pN+, 73% for a positive surgical-margin, and 83% for a negative surgical-margin. There were no statistical differences between any of these factors. However, the disease-free survival rate in pT3 patients with poorly differentiated adenocarcinoma (PDA) who received postoperative radiotherapy combined with hormonal therapy was significantly superior to that in patients with the same characteristics who received hormonal therapy (100% vs 27%; p = 0.011). The cause-specific 5-year survival rates were 100% in pT0, 100% in pT2, 92% in pT3, 50% in pT4, 94% in pN-, 93% in pN+, 93% for a positive surgical-margin, 98% for a negative surgical-margin, 100% in the aforementioned pT3 patients with PDA and postoperative radiotherapy combined with hormonal therapy and 86% in pT3 patients with PDA and postoperative hormonal therapy. There were no statistical differences between any of these factors. CONCLUSIONS: Our results suggest that radical prostatectomy is available for both organ-confined and non organ-confined advanced prostate cancer. Postoperative radiotherapy combined with hormonal therapy is especially useful for patients in pT3 with PDA.

Adenocarcinoma↗
PubMed1999

WF14861, a new cathepsins B and L inhibitor produced by Colletotrichum sp. II. Biological properties.

WF14861, 3-(N-(1-(N-(4-aminobutyl)-N-(3-aminopropyl)carbamoyl)-2-(4-hydroxyphenyl )ethyl)carbamoyl)oxirane-2-carboxylic acid, was obtained from the culture mycelium of Colletotrichum sp. as a novel cathepsins B and L inhibitor. WF14861 also showed inhibitory activities against bone derived crude protease and other cysteine proteases in vitro. The compound ameliorated the tissue damage and the bone destruction models of low-calcium-diet-fed mouse and adjuvant arthritis rat model.

Animals↗
PubMed1999

Purification and characterization of alkaline phosphatase from Bacillus stearothermophilus.

Soluble alkaline phosphatase from the thermophilic bacterium Bacillus stearothermophilus was purified by a combination of chromatographic methods, and its properties were examined. The purified enzyme had specific activity of 4.43 micromol p-nitrophenol/min per mg of protein and seemed to be a single band on SDS/PAGE with a molecular mass of 32 kDa. Its apparent Km for p-nitrophenyl phosphate was 1.114 mM. The enzyme exhibited an optimal pH of approx. 9.0 and exhibited its highest activity at 60-70 degrees C. It also showed a bivalent cation requirement for activity, with maximal enhancement in the presence of Mg2+. In addition, significant thermal stability was observed in comparison with counterparts from mesophiles. Its partial N-terminal sequence was T1FSIVAFDPATGELGIAVQ19 as estimated by automated Edman degradation method. A search on the SwissProt database did not reveal any similar protein sequences from other sources.

Alkaline Phosphatase↗