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Biomedical subjects

S Okada

Publications and source records attributed to S Okada.

At least 523 records · Page 29Linked to original sources
PubMed1996

Local recurrence of hepatocellular carcinoma after percutaneous ethanol injection.

BACKGROUND: Percutaneous ethanol injection (PEI) therapy is now widely used for small hepatocellular carcinomas (HCC). However, only limited information is available regarding local tumor recurrence after PEI treatment. METHODS: We investigated the relationship of pretreatment clinicopathologic variables (tumor size, tumor cell differentiation and tumor staining) to local recurrence in 170 PEI-treated HCC nodules (measuring 5-39 mm in greatest dimension) in 84 patients. RESULTS: Local recurrence was observed in 17 of 170 PEI-treated nodules. Among these, 13 local recurrences were observed as the first event of progression after PEI. Local recurrence rates at 1, 2, and 4 years were 6.6%, 14.2%, and 14.2%, respectively, and all recurrences were observed within 2 years after PEI. Of the 3 variables investigated, large tumor size (31 mm or larger in greatest dimension) was significantly associated with a higher local recurrence rate. CONCLUSIONS: This study demonstrated that tumor size influences the local efficacy of PEI for small HCC. Therefore, we recommend that a reasonable indication for PEI therapy is HCC lesions measuring less than 30 mm in greatest dimension.

Antineoplastic Agents↗
PubMed1996

Epidermal growth factor receptor targeting prevents uncoupling of the Grb2-SOS complex.

Insulin stimulates the Ras/Raf/MEK/ERK pathway leading to feedback phosphorylation of the Ras guanylnucleotide exchange protein SOS and dissociation of Grb2 from SOS. Even though epidermal growth factor (EGF) also stimulates ERK activity and phosphorylation of SOS similar to insulin, EGF induces a dissociation of the Grb2-SOS complex from Shc. To determine the molecular basis for this difference, we examined the signaling properties of a mutant EGF receptor lacking the five major autophosphorylation sites. Although EGF stimulation of the mutant EGF receptor activates ERK and phosphorylation of both Shc and SOS, it fails to directly associate with either Shc or Grb2. However, under these conditions EGF induces a dissociation of the Grb2-SOS complex suggesting a role for receptor and/or plasma membrane targeting in the stabilization of Grb2-SOS interaction. Consistent with this hypothesis, expression of an SH2 domain Grb2 mutant which is unable to mediate plasma membrane targeting of the Grb2-SOS complex results in both insulin- and EGF-stimulated uncoupling of Grb2 from SOS. Furthermore, a plasma membrane-bound Grb2 fusion protein remains constitutively associated with SOS. Together, these data demonstrate that EGF stimulation prevents the feedback uncoupling of Grb2 from SOS by inducing a persistent plasma membrane receptor targeting of the Grb2-SOS complex.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Effect of serum protein binding on real-time trafficking of liposomes with different charges analyzed by positron emission tomography.

Liposomes have been used as carriers of various materials and as tools for gene transfer: for the latter purpose, positively charged liposomes are usually used. To evaluate the stability in the presence of serum and the in vivo behavior of such liposomes as well as those aspects of neutral and negatively charged liposomes, we investigated liposomal agglutinability in the presence of serum, serum protein binding to these liposomes, and real-time liposomal trafficking by a non-invasive method using positron emission tomography (PET). Liposomes composed of dipalmitoylphosphatidylcholine, cholesterol without or with charged lipid were prepared in the presence of mannitol, and the turbidity change in the presence of serum was determined. Turbidity increase was not observed for so-called long-circulating liposomes, i.e., liposomes modified with glucuronic acid or with poly(ethylene glycol), or for negatively charged liposomes containing dicetyl phosphate (DCP), phosphatidylglycerol, or phosphatidylserine. On the contrary, a significant turbidity increase was observed when positively charged liposomes modified with stearylamine, stearyltrimethylammonium chloride or 1,2-dimyristyloxypropyl-3-dimethylhydroxyethyl bromide (DMRIE), which is known as a component of liposomes for gene transfer, were used. These liposomes were found to have bound a high amount of serum proteins after separation of unbound serum proteins by use of a spin column. The liposomal trafficking in vivo was determined for three kinds of liposomes, i.e., liposomes with DMRIE, those with DCP, and those without charged lipids. These liposomes were prepared in the presence of 2-[18F]fluoro-2-deoxy-D-glucose ([2-18F]FDG), and the [2-18F]FDG-labeled liposomes were administered to mice to perform PET scans. Positively charged liposomes containing DMRIE showed high accumulation in the liver compared with neutral and negatively charged liposomes. Since DMRIE-liposomes tended to aggregate in the presence of serum, and to be associated with serum protein, these characteristics may lead to the high uptake of DMRIE-liposomes by the liver.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1996

Growth hormone (GH) and a GH antagonist promote GH receptor dimerization and internalization.

It has previously been shown that a human growth hormone (hGH) analog, hGH-G120R, acts as a GH antagonist (Chen, W. Y., Wight, D. C. , Wagner, T. E., and Kopchick, J. J. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 5061-5065; Chen, W. Y., White, M. E., Wagner, T. E., and Kopchick, J. J. (1991) Endocrinology 129, 1402-1408; Chen, W. Y., Chen, N-Y., Yun, J., Wang, X. Z., Wagner, T. E., and Kopchick, J. J. (1994) J. Biol. Chem. 269, 15892-15897). In this study, we report the ability of hGH and hGH-G120R to be internalized by GH receptor expressing cells. Additionally, results of chemical cross-linking experiments revealed that both native hGH and hGH-G120R form complexes similar in size to that expected for hGH when bound to recombinant hGH-binding protein (bp). The molecular mass of the complex was determined to be approximately 280 kDa which is consistent with multiple receptors interacting with the ligand. The predominant radiolabeled band detected was a complex of approximately 140 kDa which probably represents one GH molecule bound to one GH receptor. The cross-linked complexes were not detected in the presence of excess unlabeled hGH or hGH-G120R and were not observed in cells which do not express detectable levels of GH receptors. Also, GH induced tyrosine phosphorylation of a complex of proteins of approximately 95 kDa in these cells whereas hGH-G120R did not. Thus, we have separated the hGH or hGH-G120R/GHR binding and internalization capabilities from the ability to stimulate tyrosine phosphorylation of intracellular proteins.

Animals↗
PubMed1996

Functional role of sialyl Lewis X and fibronectin-derived RGDS peptide analogue on tumor-cell arrest in lungs followed by extravasation.

Our study demonstrates that synthetic sialyl Lewis X (SLex) as a ligand for selectins and fibronectin-derived RGDS peptide analogue [Ar(DRGDS)3] inhibits lung metastases produced by i.v. co-injection of B16-BL6 melanoma cells. To investigate the inhibitory mechanisms in a living animal, we performed positron-emission tomography (PET) analysis after i.v. injection of [2-18F]2-fluoro-2v-deoxy-D-glucose-labeled tumor cells with or without liposomal SLex or Ar(DRGDS)3. The real-time PET measurement for the first 120 min, started immediately after injection, showed that tumor-cell arrest, i.e., accumulation in the target organ (lung) was remarkably inhibited by liposomal SLex, but not inhibited by Ar(DRGDS)3 or liposomal Me-SLex, which is not recognized by selectins. In contrast, Ar(DRGDS)3 inhibited the invasion of B16-BL6 cells into reconstituted basement membrane (Matrigel) following tumor arrest, whereas SLex- or Me-SLex-entrapped liposomes did not affect tumor invasion. In the metastatic processes containing tumor-cell lodgement and arrest in the target organ followed by extravasation (invasion), SLex resulted in the inhibition of initial arrest of tumor cells, presumably tumor-endothelium interaction, while Ar(DRGDS)3 achieved inhibition of tumor invasion into basement membrane at later steps of the cascade, consequently leading to inhibition of metastasis. Thus, tumor-cell arrest in lungs in the metastatic processes must be precisely and properly controlled by different adhesion molecules at different stages, which are similar to those observed in leukocyte-endothelium interaction.

Amino Acid Sequence↗
PubMed1996

Antitumor activity of vincristine encapsulated in glucuronide-modified long-circulating liposomes in mice bearing Meth A sarcoma.

Liposomes modified with the uronic acid derivative palmityl-D-glucuronide (PGlcUA) have a long circulation time and tend to accumulate in the tumors of tumor-bearing mice. Taking advantage of this character, we investigated the therapeutic effect of vincristine (VCR) encapsulated in liposomes containing PGlcUA (dipalmitoylphosphatidylcholine/cholesterol/PGlcUA = 4:4:1 as a molar ratio) on tumor-bearing mice. VCR was loaded into liposomes by a remote loading method, and then free or liposomal VCR was injected intravenously into BALB/c mice bearing Meth A sarcoma implanted subcutaneously 5 days before hand. Single-dose administration of VCR (3.0 mg/kg) in PGlcUA-liposomes significantly suppressed tumor growth, and prolonged the survival time (T/C = 1.37). Furthermore, two-dose administration of the liposomes cured one third of the animals. The therapeutic effect of PGlcUA-liposomes was greater than that of control liposomes containing dipalmitoylphosphatidylglycerol instead of PGlcUA. PGlcUA-liposomes might thus be a useful tool for delivering antitumor agents to tumor tissues.

Animals↗
PubMed1996

Potato D-enzyme catalyzes the cyclization of amylose to produce cycloamylose, a novel cyclic glucan.

Potato D-enzyme was purified from recombinant Escherichia coli, and its action on synthetic amylose (average Mr of 320,000) was analyzed. D-enzyme treatment resulted in a decrease in the ability of the amylose to form a blue complex with iodine. Analysis of the products indicated that the enzyme catalyzes an intramolecular transglycosylation reaction on amylose to produce cyclic alpha-1,4-glucan (cycloamylose). Confirmation of the cyclic structure was achieved by demonstrating the absence of reducing and nonreducing ends, resistance to hydrolysis by glucoamylase (an exoamylase), and by "time of flight" mass spectrometry. The degree of polymerization of cycloamylose products was determined by time of flight mass spectrometry analysis and by high-performance anion-exchange chromatography following partial acid hydrolysis of purified cycloamylose molecules and was found to range from 17 to several hundred. The yield of cycloamylose increased with time and reached >95%. D-enzyme did not act upon purified cycloamylose, but if glucose was added as an acceptor molecule, smaller cyclic and linear molecules were produced. The mechanism of the cyclization reaction, the possible role of the enzyme in starch metabolism, and the potential applications for cycloamylose are discussed.

Chromatography, Gel↗
PubMed1996

Separation of B-3 monodesamidoinsulin from human insulin by high-performance liquid chromatography under alkaline conditions.

The separation of human insulin (HI) and related compounds such as A-21 monodesamido HI (A-21DHI) and B-3 monodesamido HI (B-3DHI) was investigated using reversed-phase HPLC and capillary zone electrophoresis (CZE). In the case of HPLC under the usual acidic conditions, whereas A-21DHI was separately eluted, B-3DHI was included in the HI peak. Then it was found that by applying a novel ODS column resistant to alkaline conditions, a good separation of B-3DHI from HI could be achieved using an alkaline eluent, and two peaks corresponding to B-3DHI were eluted in front of the HI peak.

Chromatography, High Pressure Liquid↗
PubMed1996

Seroepidemiological study of human herpesvirus-6 and -7 in children of different ages and detection of these two viruses in throat swabs by polymerase chain reaction.

The presence of human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) in throat swabs of 62 children of different age groups (group I, ages 0-5 month; group II, ages 6-11 months, group III, ages 12-23 months, group IV, age 2-8 years) and 28 adults was detected by polymerase chain reaction. The detection rate of HHV-6 DNA was the highest (87%) in children aged 1-year-old and decreased with age, whereas the detection rate of HHV-7 increased with age and reached a maximum in adults. HHV-6B was detected in almost all samples except for two children who secreted only HHV-6A. When the antibody prevalence was determined in the four groups of children, HHV-6 antibody was detected in 8/12 (66.7%), 10/12 (83.3%), 15/16 (93.8%), and 13/14 (92.9%), respectively. Antibody to HHV-7 in these groups was detected in 6/12 (50.0%), 4/12 (33.3%), 12/16 (75.0%), and 13/14 (92.9%), respectively. Detection of HHV-6 DNA in throat swabs of triplets who had the sequential onset of exanthem subitum was attempted by using samples sequentially collected from these children after the onset of the disease in the first patient. HHV-6 DNA with high copy numbers was detectable during the acute and convalescent phases of the disease in all patients, but no DNA was detected in samples collected before the onset of disease.

Adult↗
PubMed1996

In vivo trafficking of long-circulating liposomes in tumour-bearing mice determined by positron emission tomography.

Various kinds of long-circulating liposome, such as ganglioside GM1-, polyethyleneglycol- (PEG-), and glucuronide-modified liposomes, have been developed for passive targeting of liposomal drugs to tumours. To evaluate the in vivo behaviour of such long-circulating liposomes, we investigated the liposomal trafficking, especially early trafficking just after injection of liposomes, by a non-invasive method using positron emission tomography (PET). Liposomes composed of dipalmitoylphosphatidylcholine, cholesterol, and modifier, namely, GM1, distearoylphosphatidylethanolamine (DSPE)-PEG or palmityl-D-glucuronide (PGlcUA), were labelled with [2-18F]-2-fluoro-2-deoxy-D-glucose ([2-18F]FDG), and administered to mice bearing Meth A sarcoma after having been sized to 100 nm. A PET scan was started immediately after injection of liposomes and continued for 120 min. PET images and time-activity curves indicated that PEG liposomes and PGlcUA liposomes were efficiently accumulated in tumour tissues time dependently from immediately after injection. In contrast, GM1 liposomes accumulated less in the tumour as was also the case for control liposomes that contained dipalmitoylphosphatidylglycerol (DPPG) instead of a modifier. Long-circulating liposomes including GM1 liposomes, however, remained in the blood circulation and avoided liver trapping compared with control DPPG liposomes. These data suggest that PGlcUA and PEG liposomes start to accumulate in the tumour just after injection, whereas GM1 liposomes may accumulate in the tumour after a longer period of circulation.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1996

Increased serotonin release across the coronary bed during a nonischemic interval in patients with vasospastic angina.

BACKGROUND: Platelet activation and coagulation abnormality have been observed during coronary spasm. It is crucial whether platelet activation occurs even during a nonischemic period. HYPOTHESIS: This study was designed to determine whether platelets might be activated across the coronary bed during a nonischemic interval in patients with vasospastic angina. METHODS: Plasma levels of serotonin, 6-keto-prostaglandin F1 alpha, and catecholamines in the aorta and the coronary sinus were simultaneously measured in 16 patients with vasospastic angina and 13 control patients with nonischemic heart disease. RESULTS: None of these patients showed myocardial ischemia during sampling. The difference in transcardiac plasma levels of serotonin in patients with vasospastic angina was significantly higher than that in controls (1.48 +/- 1.08 ng/ml vs. 0.07 +/- 0.12 ng/ml, respectively, p < 0.001). Coronary sinus plasma norepinephrine levels in these two groups were almost the same (204.8 +/- 110.8 pg/ml vs. 190.4 +/- 131.6 pg/ml, respectively). The ratio of 6-keto-prostaglandin F1 alpha in the coronary sinus and the aorta was not different between the two groups (1.17 +/- 0.96 in patients with vasospastic angina vs. 1.15 +/- 0.68 in controls). CONCLUSIONS: These data suggest that platelet activation across the coronary bed should be ascribed to endothelial dysfunction. Lack of compensatory enhancement of prostacyclin production might be concerned with dysfunction of coronary endothelial cells in these patients.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Immunohistochemical localization of manganese superoxide dismutase in the rat cochlea.

There has been recent increasing interest in the involvement of superoxide radicals (O2-) and their scavenging enzymes, the superoxide dismutases, in the patho-physiology of certain diseases. Since mitochondria are significant intracellular sources of O2- and important targets of oxidant injury, determining the intracochlear localization of mitochondrial O2- scavenging enzyme may provide important insight into the pathogenesis of injury due to cochlear oxidants. In order to locate the mitochondrial O2- scavenging enzyme, manganese superoxide dismutase (MnSOD), the authors used a modified immunoglobulin peroxidase bridge sequence method to detect MnSOD in paraffin-embedded, formalin-fixed rat cochleas. Site-specific immunolocalization of MnSOD could be demonstrated in the cochlear labyrinth, suggesting that the generation of intracochlear O2- was possibly implicated in the metabolically active sites and sites rich in vascularity. This study also provided a useful probe for detecting MnSOD immunohistochemically from ethylenediamine tetra-acetic acid-treated materials without requiring an antigen retrieval procedure.

Animals↗
PubMed1996

Increase in portal blood interleukin-6 soon after the commencement of digestive surgery.

To determine whether cytokines produced in the operative field during digestive surgery selectively spill over into the portal blood, the changes in interleukin-6 (IL-6) levels in portal and peripheral venous blood were assayed at several points in time from the commencement of surgery until 14 days later, in 11 patients. Similar changes in the IL-6 levels were observed in the portal and peripheral blood samples; however, the IL-6 levels in the portal blood reached a maximum 6-12h after the commencement of surgery, being earlier than in the peripheral venous blood. In fact, between 3 and 12h after the commencement of surgery, the IL-6 levels were higher in the portal blood by 33-81 pg/ml. By 24h or more after the commencement of surgery, the IL-6 levels did not differ significantly in the two types of blood samples. Moreover, the C-reactive protein levels 2 days after surgery were even more closely correlated to the maximum IL-6 levels in the portal blood than to those in the peripheral venous blood. These results suggest that IL-6 produced during intra-abdominal digestive surgery initially enters the portal blood, being trapped by IL-6 receptors in the liver, where it may regulate the synthesis of acute-phase proteins as a hepatocyte-stimulating factor.

Adult↗
PubMed1996

Allele frequencies of intragenic, and 5' and 3' markers of the dystrophin gene in Japanese families afflicted with Duchenne or Becker muscular dystrophy.

Using the polymerase chain reaction method (PCR), we examined the allele frequencies and heterozygosities of 7 polymorphic sites (pERT87, and CA polymorphisms in the 5' and 3' regions) of the dystrophin gene in 20 Japanese Duchenne muscular dystrophy and Becker muscular dystrophy (DMD or BMD) families consisting of 36 males, including 23 cases of DMD and BMD, and 28 females. The allele frequencies of three primer and enzyme sets in the pERT87 locus were well comparable to those in the previously reported Japanese female cases but different from in other countries. The frequencies of 5' markers of the dystrophin gene in Japanes were different from the reported Caucasian frequencies. As for 5'DYS-I and 5'DYS-II, the numbers of alleles in our cases were less than in Caucasians, and the heterozygosities of all three markers (5'DYS-I, II and III) were lower than in Caucasians. However, the 3'CA polymorphisms showed almost the same frequencies and heterozygosities as in Caucasians. All of our females showed a heterozygous pattern for at least one locus, with the combination of the seven markers. The usefulness of linkage analysis involving PCR methods with these intragenic, and 5' and 3' markers of the dystrophin gene in the carrier and prenatal diagnosis of DMD and BMD was confirmed by the successful prenatal diagnoses in 15 fetuses, the exception being one case considered to have a new mutation.

Alleles↗
PubMed1996

Liposomal Arg-Gly-Asp analogs effectively inhibit metastatic B16 melanoma colonization in murine lungs.

Analogs of a synthetic peptide having the L-arginine-L-glycine-L-aspartic acid (RGD) sequence have been found to decrease metastatic colonization. To enhance the metastasis-suppressing efficacy of these analogs, we sought to stabilize these analogs and to prolong their circulation time by incorporating them into a liposomal formulation. Various structures of RGD analogs grafted to hydrophobic groups were synthesized and then incorporated into liposomes. Liposomes composed of distearoylphosphatidylcholine, cholesterol, dipalmitoylphosphatidylglycerol and appropriate RGD analogs were injected intravenously along with B16BL6 murine melanoma cells into mice. Liposomal RGD (0.6 mumol of the analog equivalent to ca. 200 micrograms RGD peptides) inhibited lung colonization up to 76%. This dose is an order of magnitude lower than that for comparable inhibition reported for free RGD. Multi-dose administration of liposomal RGD (0.15 mumol of the analog) also inhibited the spontaneous lung metastasis of cells from a primary tumor site of B16BL6 cells subcutaneously implanted into the footpad of mice. Taken together, our data indicate that liposomal RGD may serve as a useful anti-metastatic agent.

Amino Acid Sequence↗
PubMed1996

Effects of various peptides on isolated rabbit lower esophageal sphincter.

Strips of lower esophageal sphincter (LES) from rabbits were tested for their responses to several peptides, and to electrical field stimulation (EFS) under the presence of some peptides. Substance P (SP), motilin, and bombesin induced contraction, and vasoactive intestinal peptide (VIP) induced relaxation. SP- and bombesin-induced contractions were antagonized by SP antagonist. VIP-induced relaxation was antagonized by phentolamine and VIP antagonist. Pretreatment with atropine, phentolamine, and diphenhydramine antagonized the motilin- and bombesin-induced contraction. Pretreatment with tetrodotoxin (TTX) attenuated the motilin- and bombesin-induced contraction, but not the SP-induced contraction and VIP-induced relaxation. EFS induced contraction, which was attenuated by TTX. Calcitonin gene-related peptide and neuropeptide Y had no effect on LES; however, they attenuated EFS-induced contraction. These findings suggest some characteristic peptidergic involvement in rabbit LES smooth muscle.

Animals↗
PubMed1996

MR findings and neurologic manifestations in Lowe oculocerebrorenal syndrome.

Two patients with oculocerebrorenal syndrome are described. Both had abnormal findings on electroencephalography and developed seizure episodes. Although Patient 2 manifested abnormal electroencephalographic findings at the age of 6 years, he did not develop seizures until the age of 9 years. Phenytoin was effective for controlling seizures in both patients. On magnetic resonance examination, there were two different types of lesions. The first lesion manifested high intensity on both T2- and proton density-weighted images, suggesting gliosis or demyelination. The second lesion manifested definitely low signals on both T1- and proton density-weighted images, implying a cystic lesion. However, these lesions on magnetic resonance examination were not correlated with the severity of clinical manifestations.

Adolescent↗