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Biomedical subjects

S Oka

Publications and source records attributed to S Oka.

At least 217 records · Page 12Linked to original sources
PubMed1997

Stimulatory effect of gangliosides on phagocytosis, phagosome-lysosome fusion, and intracellular signal transduction system by human polymorphonuclear leukocytes.

Gangliosides are known to be differentiation-inducing molecules in mammalian stem cells. We studied the interaction between the molecular structure of glycosphingolipids (GSLs) and their promoting mechanisms of the phagocytic processes in human polymorphonuclear leukocytes (PMN). The effect of various gangliosides from mammalian tissues on adhesion, phagocytosis, phagosome-lysosome (P-L) fusion and superoxide anion production was examined by human PMN using heat-killed cells of Staphylococcus aureus-coated with GSLs. Gangliosides GM3, GD1a, GD3 and GT1b showed a marked stimulatory effect on the phagocytosis and P-L fusion in a dose-dependent manner, while ganglioside GM1, asialo GM1 and neutral GSLs did not. The relative phagocytic rate of ganglioside GM3-coated S. aureus was the highest among the tested GSLs. Both P-L fusion rate and phagocytosis of S. aureus were elevated significantly when coated with ganglioside GD1a, GD3 or GT1b, and GT1b gave a five times higher rate than that of the non-coated control. These results suggest that the terminal sialic acid moiety is essential for the enhancement of phagocytosis and that the number of sialic acid molecules in the ganglioside is related to the enhancement of the P-L fusion process. On the other hand, the superoxide anion release from PMN was not affected by ganglioside GM2, GM3, GD1a or GT1b. Furthermore, to clarify the trigger or the signal transduction mechanism of phagocytic processes, we examined the effect of protein kinase inhibitors such as H-7, staurosporine (protein kinase C inhibitor), H-89 (protein kinase A inhibitor), genistein (tyrosine kinase inhibitor), ML-7 (myosin light chain kinase inhibitor), and KN-62 (Ca2+/calmodulin-dependent protein kinase II inhibitor) on ganglioside-induced phagocytosis. H-7, staurosporine and KN-62 inhibited ganglioside-induced phagocytosis in the range of concentration without cell damage, while H-89, genistein and ML-7 did not. Moreover, H-7 and KN-62 inhibited ganglioside-induced P-L fusion. These results suggest that protein kinase C and Ca2+/calmodulin-dependent protein kinase II may be involved in the induction of phagocytosis and P-L fusion stimulated by gangliosides.

Bacterial Adhesion↗
PubMed1997

In vivo induction of apoptosis in the thymus by administration of mycobacterial cord factor (trehalose 6,6'-dimycolate).

It is reported that some bacteria or bacterial components cause thymic atrophy via the apoptotic process. The present study demonstrated for the first time in vivo induction of apoptosis in the mouse thymus by mycobacterial cord factor (CF) (trehalose 6,6'-dimycolate). When 300 microg of purified CF from Mycobacterium tuberculosis was intravenously administered to BALB/c mice in the form of water-in-oil-in-water (w/o/w) emulsion, thymic atrophy and pulmonary granulomas were induced with a peak on day 7, whereas, in the form of liposomes, CF induced thymic atrophy on days 14 to 21 in parallel with the development of hepatic granulomas. Thymic atrophy resulted from the depletion of cortical lymphocytes via apoptosis as revealed by DNA fragmentation and karyorrhectic changes. In contrast, mycobacterial sulfatide (2,3,6,6'-tetraacyl trehalose 2'-sulfate) caused neither thymic atrophy nor granuloma formation. Compared to lipopolysaccharide-induced thymocyte apoptosis, CF (w/o/w)-induced thymocyte apoptosis developed more slowly, reached a maximum later, and lasted longer but was less intense. Although serum tumor necrosis factor alpha (TNF-alpha) levels in CF-treated mice were not significantly elevated, administration of anti-TNF-alpha antibody almost completely inhibited thymic atrophy and granuloma formation. Serum corticosterone levels were only slightly elevated by CF administration. The present results indicate that mycobacterial CF induces thymic atrophy via apoptosis, which is closely linked with granuloma formation.

Animals↗
PubMed1997

Abrogation of in vitro suppression of human immunodeficiency virus type 1 (HIV-1) replication mediated by CD8+ T lymphocytes of asymptomatic HIV-1 carriers by staphylococcal enterotoxin B and phorbol esters through induction of tumor necrosis factor alpha.

CD8+ T lymphocytes of asymptomatic human immunodeficiency virus type 1 (HIV-1) carriers (AC) suppress HIV-1 replication in vitro. Failure of host defense mechanisms and increased virus proliferation are associated with disease progression. The exact mechanisms inducing these changes at the advanced stage of the disease are still obscure. In this study, we searched for experimental conditions favoring the abrogation of the suppression of viral replication in peripheral blood mononuclear cells (PBMC) of AC by using various pharmacological and biological probes modifying cell activation. Among such agents, staphylococcal enterotoxin B (SEB) and phorbol 12-myristate 13-acetate (PMA) markedly increased otherwise low levels of HIV-1 replication in cultures of phytohemagglutinin-stimulated AC PBMC following in vitro HIV-1 LAI infection. A similar but less pronounced virus induction was also observed in macrophage-tropic HIV-1. Individual pretreatment of CD4+ and CD8+ PBMC fractions with these agents caused a reduction in CD8+ cell proliferation and enhanced HIV-1 replication in CD4+ cells. SEB- and PMA-mediated augmentation of HIV-1 replication in AC PBMC was significantly blocked by neutralizing antibody to tumor necrosis factor-alpha (TNF-alpha), although recombinant TNF-alpha alone failed to reproduce the effects of SEB or PMA. Our results suggest that the induction of TNF-alpha may be one of the mechanisms that overcomes the CD8+-induced suppression of HIV-1 replication in AC and that it may induce HIV-1 replication.

Antibodies↗
PubMed1997

In vivo sequence variability of human immunodeficiency virus type 1 envelope gp120: association of V2 extension with slow disease progression.

According to the rate of depletion of CD4 cell counts, we grouped 12 cases of human immunodeficiency virus type 1 (HIV-1) infection as 6 rapid (21.0 to 33.8 cells per microl per month) and 6 slow (0.9 to 7.9 cells per microl per month) progressors and determined the individual viral quasispecies patterns by sequencing the genome region encoding the V1, V2, and V3 loops of envelope protein. Although the quasispecies structures varied widely from one individual to another, a strong correlation was observed between a low rate of disease progression and a high degree of genetic diversity of HIV-1. Furthermore, the V2 loop extension was observed specifically in individuals with slow or no disease progression, whereas basic amino acid substitutions in V3 characteristic of a viral phenotype shift from non-syncytium inducing to syncytium inducing were observed in patients with advanced stages of disease regardless of their rate of disease progression. Studies with recombinant viruses suggested that elongation of V2 potentially restricts the capacity of HIV-1 to replicate in macrophages. Thus, our results suggest the association of distinct sequence features of both V3 and V2 with particular patterns of disease progression. Elongation of the V2 loop may be a good predictor of slow disease progression, while basic substitutions of V3 without elongation of V2 are characteristic of rapid progression.

Amino Acid Sequence↗
PubMed1997

A monoclonal antibody recognizing nestin and the phosphorylated form of neurofilament-M.

In the course of an immunohistochemical screening of antibodies raised against a postnatal day 7 rat brain membrane fraction, we obtained a monoclonal antibody that recognizes both neurofilament-M, a type VI intermediate filament protein, and nestin, a type IV intermediate filament protein. In newborn rat cerebellum, the 5A7 antibody stained Bergmann glial fibers and subsets of axons simultaneously, but in adult cerebellum it only stained neuronal elements. Upon immunoblot analysis of neonatal rat cerebellum, 5A7 gave two prominent bands corresponding to 140 and > 200 kDa. The former was identified as neurofilament-M and the latter as nestin. Dephosphorylation of neurofilament-M resulted in a dramatic reduction in the immunoreactivity, indicating that 5A7 recognized the phosphorylated form of neurofilament-M. Immunoblot analysis of V8 protease digests of neurofilament-M revealed that the epitope on neurofilament-M is located on the carboxy-half of the tail domain of neurofilament-M. These results indicate that 5A7 is the first monoclonal antibody which recognizes a common or similar epitope on different classes of intermediate filament proteins other than the conserved rod domain. The presence of a common or similar epitope on both nestin and neurofilament-M recognized by 5A7 may suggest the possibility that nestin and neurofilament-M have a common functional motif.

Animals↗
PubMed1997

In vitro and ex vivo anti-human immunodeficiency virus (HIV) activities of a new water-soluble HIV protease inhibitor, R-87366, containing (2S,3S)-3-amino-2-hydroxy-4-phenylbutanoic acid.

In a series of compounds containing (2S,3S)-3-amino-2-hydroxy-4-phenylbutanoic acid (AHPBA), a transitionstate mimetic, R-87366:(2S,3S)-3-[N-(quinoxaline-2-carbonyl)-L-asparaginyl]amino- 2-hydroxy-4-phenylbutanoyl-L-proline tert-butylamide, was found to be a potent human immunodeficiency virus protease inhibitor (Ki value was 11 nM) and anti-HIV agent (IC90 value was 0.5 microM for HIV-1IIIB acutely infected cells) with moderate water-solubility (4.2 mg/ml at 25 degrees C). The compound was also active in chronically infected Molt-4/HIV-1IIIB cells, and inhibited the proteolytic processing of p55 into p17, suggesting that its anti-HIV activity was derived from HIV protease inhibition. The compound showed more potent activity (IC90 value was 0.03-0.25 microM) against clinical isolates of HIV in 5 out of 6 patients examined with varying clinical status in an ex vivo assay. One isolate, however, from the sixth patient, was less sensitive to R-87366 (IC90 value was 0.5 microM). In experiments with this strain, R-87366 showed comparatively low efficacy in acutely infected peripheral blood mononuclear cell (PBMC). This result suggests that the diversity of sensitivity shown in the ex vivo assay could be caused by the viral property itself. As a result of the determination of nucleic acid sequences in the clinical isolates, some amino acids were found to be substituted in the protease region, in contrast to the HIV-1 clade B consensus sequence, and some of them have been reported to contribute to the susceptibility of HIV protease inhibitors.

Amino Acid Sequence↗
PubMed1997

A case of acute myocardial infarction due to primary coronary dissection.

A case of acute myocardial infarction associated with primary coronary dissection was followed up angiographically. A 46-year-old woman complained of chest oppression. Electrocardiogram on admission showed ST-segment elevation in V1-5. Urgent coronary angiography was performed under a diagnosis of acute anterior myocardial infarction, and showed a significant stenosis with multiple filling defects in segments 7-8 (99% with severe delay) in the left anterior descending artery. There was no organic lesion in the right coronary artery. Intracoronary thrombolytic therapy was unsuccessful, and thereafter she was treated with aspirin, warfarin and isosorbide dinitrate. Coronary angiography performed 1 month later revealed a long dissection with double lumens in segments 7-8. The septal branches emerged from the smaller lumen. Two months later, the 2 lumens were almost equal in size. These findings indicated that coronary dissection produced a false lumen with an entry in segment 7 and a reentry in segment 8, and that the false lumen was responsible for the greater flow. Four months later, the flow in the true lumen had improved remarkably while that in the false lumen had almost disappeared. She remained in stable condition during the follow-up period of 4 months.

Aortic Dissection↗
PubMed1997

Inhibitory effect of alginic acids on hyaluronidase and on histamine release from mast cells.

The effects of various types of alginic acid consisting of L-guluronic acids (G) and D-mannuronic acids (M) on hyaluronidase and mast cell degranulation were examined. Alginic acid with an M/G ratio of 1.0 exhibited the strongest inhibition of both activities, the higher molecular weight alginic acids of 150 to 370 kDa being preferable in both cases. Esterification of the carboxyl residue enhanced the latter activity.

Alginates↗
PubMed1997

CD8+ T lymphocyte counts as an adjunctive predictor of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome.

We encountered a case of cytomegalovirus (CMV) retinitis with spontaneous regression in association with an increased number of CD8+ but not CD4+ T lymphocytes in a patient with acquired immunodeficiency syndrome (AIDS). Thus, we examined the number of CD4 and CD8 counts at the diagnosis of CMV retinitis and compared with those of Pneumocystis carinii pneumonia (PCP). All 21 patients with a confirmed diagnosis of PCP (22 episodes) and 14 CMV retinitis patients were included in this study. Although PCP occurred after depletion of CD4 count to below 200/microl, CD8 count at that time varied widely and remained normal in some patients (median: 276.5/microl, range: 133-900/microl). In contrast, as CMV retinitis occurred after further depletion of CD4 count to below 50/microl, CD8 count decreased to below 500/microl (median: 238/microl, range: 43-448/microl) (p<0.05; PCP vs CMV retinitis). The values of the sensitivity and specificity for CMV retinitis obtained at the cutoff point of either 400/microl in CD8 count and 50/microl in CD4 count were similar. When these two cutoff points were combined, the positive predictive value was 46%. Monitoring of CD8 count may prove valuable as an additional predictor of CMV retinitis in patients with AIDS after CD4 depletion.

AIDS-Related Opportunistic Infections↗
PubMed1997

Helicobacter pylori inhibits the secretory activity of gastric parietal cells in patients with chronic gastritis. An ultrastructural study.

BACKGROUND: Previous in vitro studies suggested that Helicobacter pylori may inhibit the acid secretion of gastric parietal cells. The aim of this study was to investigate ultrastructurally the influence of H. pylori infection on the gastric parietal cell function in vivo. METHODS: This study comprised 28 patients with chronic gastritis. Biopsy specimens were taken from the gastric body in all cases and examined by electron microscopy. Gastric parietal cells were counted in each ultrathin section and classified into secretory and non-secretory types. The pH of the gastric juice was also measured in all patients. RESULTS: The number of parietal cells in the secretory phase was significantly lower in H. pylori-infected (n = 16) patients than in those (n = 12) without H. pylori infection. The intragastric pH was significantly higher in patients with H. pylori-associated gastritis than in those without H. pylori infection. Parietal cells in secretory phase tended to decrease in proportion to the activity of the gastric mucosal inflammation. CONCLUSIONS: The results of this investigation suggests that H. pylori-associated gastritis is related to a decreased secretory activity of the gastric parietal cells.

Biopsy↗
PubMed1997

In vivo sequence changes of HIV-1 envelope V2 and V3 loops.

Human immunodeficiency virus type 1 (HIV-1) circulates in vivo as heterogeneous mixed populations (quasispecies). We analyzed the quasispecies nature of the first, second, and third hypervariable loops (V1, V2, and V3) of the gp 120 in plasma and viral isolates obtained from 19 infected individuals. Sequence analysis of 7 SI and 10 NSI isolates showed that the increased positive charge in V3 and elongation of V1 clearly correlated with viral SI capability in PBMC. Contrary to the previous report (M. Groenink et al. Science 260: 1513-1525, 1993), there appeared to be no correlation between SI or non-SI phenotype and length of V2. However, all the 5 isolates with long V2 and basic V3 showed SI phenotype, whereas 4 out of 6 isolates with short V2 and basic V3 showed NSI phenotype, still suggesting some functional cooperation of V2 and V3 on viral syncytium inducing capability. Sequence analysis of HIV-1 in plasma showed the positive correlation between V3 charge and V1 or V2 length in 4 cases. This result suggests the associated evolution of V1/V2 and V3 in these cases.

Cloning, Molecular↗
PubMed1997

Dual phasic suppression of viral replication following de novo human immunodeficiency virus type 1 (HIV-1) infection in lymphocytes of asymptomatic HIV-1 carriers.

Replication of human immunodeficiency virus type 1 (HIV-1) is suppressed in asymptomatic HIV-1 carriers (ACs). By using an in vitro experimental system, the mechanism of this suppression was investigated. Following in vitro infection of a laboratory HIV-1 strain, the peripheral blood mononuclear cells (PBMC) of ACs transiently supported a low level of viral replication, then the virus production rapidly decreased. PCR analysis revealed that HIV-1 proviral DNA integrated in the PBMC of ACs following infection gradually decreased. Such tapering consequences of in vitro HIV-1 infection in the PBMC of ACs were abrogated by depletion of CD8+ T cells from the culture. Furthermore, the viruses subsequently produced by the PBMC of an AC were less able to replicate than the virus produced by CD8+ cell-depleted PBMC of the same donor. These observations suggested that the CD8+ T cell-mediated suppression of HIV-1 replication in ACs may involve both cytocidal and cytostatic mechanisms: the former kills the cells producing viruses, and the latter inhibits viral spread by reducing viral infectivity.

CD8-Positive T-Lymphocytes↗
PubMed1997

Timing and side effects of flumazenil for dental outpatients receiving intravenous sedation with midazolam.

We studied the timing and side effects of flumazenil treatment for 10 healthy volunteers and 46 dental outpatients who received intravenous sedation with midazolam. For the volunteers, vital signs were monitored before and after intravenous injection of midazolam and flumazenil. In addition, grip strength, signs and symptoms, and performance on the Romberg's test and addition tests were evaluated 30 min and 60 min after midazolam injection as well as after flumazenil injection. There were no significant changes in vital signs before, immediately after, or 50 min after injection of flumazenil, the latter time corresponding to the half-life of the drug. Thus, awakening from sedation was associated with no effects on the cardiovascular or respiratory systems. Distinct effects of flumazenil were demonstrated by the Romberg's test and the assessment of sedation status. Flumazenil had no effect on the outcome of the addition test. For the outpatients, sedation status and signs and symptoms were studied in patients undergoing procedures lasting 30 min or less (group S) and those undergoing procedures lasting 31 to 60 min (group L). Three patients in group S and one in group L had signs and symptoms of resedation. After treatment with flumazenil, abnormalities such as excitability and nausea were reported by only two patients in group L. One patient in group S had drowsiness that did not resolve after injection of flumazenil and continued until the following day. Our results indicate that flumazenil should be given at least 60 min after intravenous sedation with midazolam in dental outpatients. Moreover, caution should be exercised with regard to the potential side effects of flumazenil.

Adult↗
PubMed1997

Comparison of lidocaine with and without bupivacaine for local dental anesthesia.

The purpose of this study was to investigate the effectiveness of a combination of bupivacaine and lidocaine and that of lidocaine alone for local dental anesthesia. First, on different days, healthy volunteers were given 2% lidocaine with 1/80,000 epinephrine or 2% lidocaine with 1/80,000 epinephrine + 0.5% bupivacaine, after which pain was produced with a pulp tester. No difference was found in the time until onset of anesthetic effect between the preparations. However, the duration of anesthetic effect was longer with both lidocaine and bupivacaine than with lidocaine alone. Next, patients undergoing dental surgery were given one of the anesthetic preparations, after which serum concentrations of the anesthetics and epinephrine were measured. The maximal serum concentration of lidocaine was higher and was reached sooner after injection in patients receiving lidocaine alone (1.74 microgram/ml after 5 min) than in patients receiving both anesthetics (0.85 microgram/ml after 3 min). The mean maximal serum concentration of lidocaine was higher in patients receiving lidocaine alone (1.77 +/- 0.03 microgram/ml) than in those receiving both anesthetics (0.99 +/- 0.45 microgram/ml). Furthermore, the mean plasma concentration of epinephrine 1 min after injection was significantly higher in patients receiving lidocaine alone (0.671 ng/ml) than in patients receiving both lidocaine and bupivacaine (0.323 ng/ml). The results of this study suggest that the combination of lidocaine with epinephrine and bupivacaine produces lower systemic levels of the anesthetic and epinephrine and a longer duration of activity than lidocaine with epinephrine alone for local dental anesthesia.

Adolescent↗
PubMed1996

Ontogenetic changes in neuropeptide Y-like-immunoreactivity in the terminal nerve of the chum salmon and the cloudy dogfish, with special reference to colocalization with gonadotropin-releasing hormone-immunoreactivity.

We observed ontogenetic changes of neuropeptide Y (NPY)-like-immunoreactivity in the terminal nerve (TN) of the chum salmon, a teleost, and the cloudy dogfish, an elasmobranch. In the chum salmon, NPY-like-immunoreactive (NPY-IR) cells first appeared in the olfactory placode of embryos at 16 days after fertilization, and then extended sequentially and centrally in the olfactory system. Colocalization of NPY- and gonadotropin-releasing hormone (GnRH)-like-immunoreactivities was also observed in TN ganglion cells. In the cloudy dogfish, NPY-IR cells first appeared in the rudimental TN ganglion of the embryo at the 40 mm stage. Then, the NPY-IR cells and fibers in the TN system increased in density during late embryonic periods. Colocalization of NPY- and GnRH-like-immunoreactivities in TN ganglion cells was not found in the developing or the adult dogfish.

Age Factors↗
PubMed1996

Overexpression of MP41 gene in a transformed endothelial cell line correlates with the increased fibronectin expression and a decreased incidence of tumorigenicity.

mp41 gene, which was originally identified as a gene regulated by the circadian clock, showed some similarity with yeast cell cycle regulator, CDC25, and its mRNA expression is restricted mainly to non-dividing cell. To elucidate the growth regulatory of mp41, mp41 cDNA was transfected into a transformed human endothelial cell line. All stable mp41 transformants showed increased levels of fibronectin expression and reduced migratory activity in vitro. Although the in vitro growth rate of mp41 transformants and their ability to grow in soft agar were not significantly altered, their tumor formation was suppressed significantly in nude mice. The results imply that mp41 gene overexpression altered the tumorigenicity associated with fibronectin elevation in stable transformation of the transformed endothelial cell line.

Animals↗