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H Okada

Publications and source records attributed to H Okada.

At least 361 records · Page 20Linked to original sources
PubMed1997

One- and three-month release injectable microspheres of the LH-RH superagonist leuprorelin acetate.

The biodegradable polymers poly(lactic/glycolic acid) (PLGA) and poly(lactic acid) (PLA) were used as wall materials in the preparation of microspheres (msp) containing the LH-RH superagonist leuprorelin (leuprolide) acetate. A novel W/O/W emulsion-solvent evaporation method was devised for the preparation of msp containing this water-soluble peptide. This method achieved high entrapment efficiency and sustained drug release over a long period predominantly due to polymer bioerosion. The msp are fine microcapsules with polycores containing the peptide at a high concentration and are easily injectable through a conventional fine needle. Leuprorelin msp made with PLGA(75/25)-14,000 or PLA-15,000 released the drug in a zero-order fashion, maintained constant serum drug levels and attained persistent objective suppression of the pituitary-gonadal system ('chemical castration') over 1 or 3 months after i.m. or s.c. injection into animals. These results indicate that depot formulations may be potentially useful in the therapy of endocrine diseases in humans. In this paper, studies on the formulation, drug release and pharmacological effects in animals for these leuprorelin depot formulations are reviewed.

Journal Article↗
PubMed1997

HIV-1 Nef protein-induced apoptotic cytolysis of a broad spectrum of uninfected human blood cells independently of CD95(Fas).

The Nef protein of HIV-1 binds to uninfected CD4+T lymphocytes and induces apoptotic cytolysis of the cells. We examined several human blood cell lines and peripheral blood mononuclear cells (PBMCs) for Nef-induced apoptotic cell death. Soluble Nef protein was shown to bind to the cell surface of not only CD4+T cells but also CD8+T lymphocytes, B lymphocytes, macrophages and neutrophils. PBMCs from normal subjects resisted Nef binding, and activation of the cells with phytohemagglutinin or concanavalin A converted the cells to be susceptible to the binding. Cross-linking of the Nef proteins bound to the cell surfaces with anti-Nef antibody-induced apoptotic cytolysis of the cells. The Nef-mediated apoptosis occurred independently of CD95(Fas). These results suggest that soluble Nef protein, which is found in sera of HIV-1 infected patients, is involved in the destruction of a broad spectrum of uninfected blood cells leading to immune suppression.

Apoptosis↗
PubMed1997

High induction of phenol UDP-glucuronosyltransferase in the kidney medulla of beta-naphthoflavone-treated rats.

Phenol UDP-glucuronosyltransferase activity was highly induced in the microsomes of the kidney medulla of rats by beta-naphthoflavone treatment. In the medulla, phenol UDP-glucuronosyltransferase and its mRNA were greatly increased in both immunoblotting and Northern blot analyses following beta-naphthoflavone treatment of the rats. In untreated rat kidneys, phenol UDP-glucuronosyltransferase was detected by immunohistochemical analysis only in proximal convolution tubular cells located in the cortex. After beta-naphthoflavone treatment of the rats, UDP-glucuronosyltransferase appeared in the epithelial cells in the straight portion of the distal tubules located in the medulla. In conclusion, the medullary distal tubular cells have high latent glucuronidation activity and are thought to play an important role in drug excretion.

Animals↗
PubMed1997

Deletion of SHIP or SHP-1 reveals two distinct pathways for inhibitory signaling.

Two signaling molecules have been implicated in the modulation of immune receptor activation by inhibitory coreceptors: an inositol polyphosphate 5'-phosphatase, SHIP, and a tyrosine phosphatase, SHP-1. To address the necessity, interaction, or redundancy of these signaling molecules, we have generated SHP-1- or SHIP-deficient B cell lines and determined their ability to mediate inhibitory signaling. Two distinct classes of inhibitory responses are defined, mediated by the selective recruitment of SHP-1 or SHIP. The Fc gammaRIIB class of inhibitory signaling is dependent on SHIP and not SHP-1; conversely, the KIR class requires SHP-1 and not SHIP. The consequence of this selective recruitment by inhibitory receptor engagement is seen in BCR-triggered apoptosis. SHP-1-mediated inhibitory signaling blocks apoptosis, while SHIP recruitment attenuates a proapoptotic signal initiated by Fc gammaRIIB.

Animals↗
PubMed1997

Recovery of leukocyte function after super-high-dose chemotherapy with peripheral blood stem cell transplantation in testicular cancer patients.

Leukocyte functions (superoxide production and phagocytosis) were evaluated in patients with testicular cancer who had undergone super-high-dose chemotherapy (SHDT) with peripheral blood stem cell transplantation (PBSCT). In 5 patients with advanced or relapsed testicular cancer who received 8 cycles of SHDT with PBSCT, we measured superoxide production activity by phorbol myristate acetate (PMA) stimulation, as well as phagocytic activity using latex particles before and after PBSCT. The median time to reach a leukocyte count of > or = 1,000/microl was 9 days after PBSCT. Superoxide production activity was significantly decreased on day 7 compared with the pre-chemotherapy level. However, it recovered by day 12 and sustained such a level thereafter. Phagocytic activity was within the normal range on day 7 but declined slightly on days 12 and 21 compared with the pre-chemotherapy level. Our results indicate that leukocyte function and leukocyte count recover promptly following PBSCT and that PBSCT is a safe and convenient adjunctive therapy after SHDT for patients with advanced testicular cancer.

Adult↗
PubMed1997

Role of a sialyl Lewis(x)-like epitope selectively expressed on vascular endothelial cells in local skin inflammation of the rat.

The role of the inducible L-selectin ligand was studied in complement-dependent acute dermatitis in rats. Although mAbs against typical sialyl Lewis(x) (CSLEX-1 and SNH-3) did not react with skin venules, a sialyl Lewis(x)-like epitope defined by mAb 2H5 (2H5-Ag) was de novo expressed on the endothelial cells of skin venules in the area of inflammation. Expression of 2H5-Ag increased concomitantly with the progression of inflammation. 2H5-Ag was identified at the 75-, 150-, and 180-kDa bands when inflammatory skin tissue was analyzed by Western blotting. In contrast, P- and E-selectins were not detectable. The role of 2H5-Ag in this model was studied in in vitro and in vivo methods. First, 2H5 was i.v. injected 15 min before induction of dermatitis. 2H5 bound to skin venules and significantly reduced the neutrophil infiltration and plasma protein leakage. In contrast, CSLEX-1, mAb ARP2-4 (P-selectin blocker), or mAb ARE-5 (E-selectin blocker) had no effects. Second, adhesion of isolated rat neutrophils to the inflammatory skin section was inhibited significantly when the sections, but not neutrophils, were preincubated with 2H5. Third, fluorescein-labeled normal rat neutrophils were injected into a rat 10 h after induction of dermatitis. The number of labeled neutrophils infiltrated into the inflammatory site was reduced significantly when they were preincubated with HRL-3 (blocking mAb against rat L-selectin), but not with 2H5 or HRL-4 (nonblocking mAb against rat L-selectin). These data show that de novo expressed 2H5-Ag/L-selectin adhesion pathway contributes to the development of acute complement-dependent inflammation in the skin.

Animals↗
PubMed1997

Hematopoiesis in the fetal liver is impaired by targeted mutagenesis of a gene encoding a non-DNA binding subunit of the transcription factor, polyomavirus enhancer binding protein 2/core binding factor.

The Pebpb2 gene encodes a non-DNA binding subunit of the heterodimeric transcription factor, polyomavirus enhancer binding protein 2/core binding factor (PEBP2/CBF), and is rearranged in inversion of chromosome 16 associated with human acute myeloid leukemia. To investigate its physiological function, Pebpb2 was mutated by a targeting strategy to generate a null mutant. The homozygous mutation in mice proved lethal in embryos around embryonic day 12.5, apparently due to massive hemorrhaging in the central nervous system. In addition, definitive hematopoiesis in the liver was severely impaired. The observed phenotype was indistinguishable from that reported for homozygous disruption of AML1, which encodes a DNA binding subunit of PEBP2/CBF. Thus, the results indicate that the two subunits function together as a heterodimeric PEBP2/CBF in vivo and that PEBP2/CBF plays an essential role in the development of definitive hematopoiesis.

Animals↗
PubMed1997

Distribution of epithelial-specific antigen in uterine cervix with endocervical glandular dysplasia.

The natural history of cervical adenocarcinoma is largely unknown, and whether endocervical glandular dysplasia is a precursor lesion to malignant tumor formation is a controversial issue. The aim of this study was to clarify the relationship of endocervical glandular dysplasia to the uterine endocervical adenocarcinoma. Thirty-one cases of glandular abnormalities of the uterine cervix were identified histologically from January 1984 to April 1992. These included 11 cases of endocervical glandular dysplasia, 5 cases of adenocarcinoma in situ, 4 cases of microinvasive adenocarcinoma, and 11 cases of invasive adenocarcinoma. The immunohistochemical localization of epithelial-specific antigen (ESA) was examined in these cases of endocervical glandular dysplasia and related lesions, and was compared to 10 normal endocervical specimens. ESA immunoreactivities were usually present in the basolateral membrane of endocervical cells in the normal endocervix. However, the expressions of ESA were increasing from the basolateral membrane to the diffuse cytoplasmic membrane, along with the malignant transformation of the endocervical cells, in 6 of 11 cases with glandular dysplasia, in 9 of 9 cases with in situ and microinvasive adenocarcinomas, and in 11 of 11 cases with invasive adenocarcinomas. This finding indicates that ESA is a useful marker for endocervical glandular dysplasia and related lesions with malignant transformation, and suggests that endocervical glandular dysplasia may be a precursor lesion to uterine cervical adenocarcinomas.

Adenocarcinoma↗
PubMed1997

Immunohistochemical analysis of intercellular adhesion molecule-1 expression in human gastric adenoma and adenocarcinoma.

In this study, we examined the distribution of intercellular adhesion molecule-1 (ICAM-1) in gastric adenomas and carcinomas immunohistochemically at the light and electron microscopic levels. ICAM-1 was expressed on tumour cells in 12 of 28 gastric carcinomas and in 3 of 11 adenomas but not on most normal gastric epithelial cells. ICAM-1 was localized on luminal sites of neoplastic glands in adenomas and in intestinal-type carcinomas, and rarely on the surface of tumour cells of diffuse carcinomas. Expression of ICAM-1 on the tumour cells was more frequent in intestinal-type than diffuse carcinomas (P < 0.005). At the ultrastructural level, ICAM-1 was present prominently on the apical membrane and weakly on the lateral surface of the tumour cells of the intestinal-type carcinoma and also localized on the perinuclear membrane and the membrane of the endoplasmic reticulum of cancer cells. There was no significant association between ICAM-1 expression and HLA antigen expression or the number of infiltrating lymphocyte subsets. These results may implicate the synthesis of ICAM-1 by gastric cancer cells, but the expression is infrequent and may not be sufficient for host immune surveillance of the tumour cell.

Adenocarcinoma↗
PubMed1997

Membrane attack complex of complement and 20 kDa homologous restriction factor (CD59) in myocardial infarction.

In order to investigate the mechanism of deposition of the complement membrane attack complex (MAC) in cardiomyocytes in areas of human myocardial infarction, the 20 kDA homologous restriction factor of complement (HRF20; CD59) and complement components (Clq. C3d and MAC) were analysed immunohistochemically using specific antibodies. Myocardial tissues obtained at autopsy from nine patients who died of acute myocardial infarction were fixed in acetone and embedded in paraffin. The ages of the infarcts ranged from about 3.5 h to 12 days. In cases of myocardial infarction of 20 h or less, MAC deposition was shown in the infarcted cardiomyocytes without loss of HRF20. Where the duration was 4 days or more, the cardiomyocytes with MAC deposition in the infarcted areas also showed complete loss of HRF20. Outside the infarcts, HRF20 in the cardiomyocytes was well preserved without MAC deposition. The present study suggests that the initial MAC deposition in dead cardiomyocytes can occur as a result of degradation of plasma-membrane by a mechanism independent of complement-mediated injury to the membrane. Loss of HRF20 from dead cardiomyocytes may not be the initial cause of MAC deposition, but may accelerate the deposition process of MAC in later stages of infarction.

Aged↗
PubMed1997

Cervical cord ependymoma with numerous microrosettes.

"Microrosette ependymoma," which is ependymoma with numerous microrosettes throughout the tumor, has rarely been reported. We describe an autopsy case of cervical cord ependymoma with two unusual features: the presence of numerous microrosettes and the formation of trabecular architecture. The tumor originated in the C2 segment of a man aged 23 years and gradually expanded over the following 15 years and 10 months until the entire cervical cord was involved. Beside the low grade of malignancy, the tumor cells exhibited a strong tendency to form microrosettes and trabecular architecture, which formed many perivascular pseudorosettes. The microrosettes mostly consisted of only two or a few more cells, in the absence of large rosettes. Thus the constituent cells were those forming perivascular pseudorosettes. Electron microscopy and immunohistochemistry characterized the ependymal properties of the microrosettes, whose lumina frequently contained fibril bundles similar to those of the Reissner's fiber fibrils, in addition to cilia and microvilli. The pathogenesis of the occurrence of numerous microrosettes is unknown; however, a defect in the mechanism of regulation of rosette formation and enlargement is the most likely explanation.

Adult↗
PubMed1997

Assessment of technetium-99m Technegas scintigraphy for ventilatory impairment in pulmonary emphysema: comparison of planar and SPECT images.

Pulmonary emphysema can be diagnosed easily by X-ray CT (CT) as a low attenuation area. Recently Tc-99m-Technegas (Technegas) has been used for ventilation scintigraphy. The present study was undertaken to assess the usefulness of planar and SPECT images by using Technegas scintigraphy in patients with pulmonary emphysema. Technegas scintigraphy, CT and pulmonary function tests were performed in 20 patients (males, age 32-78 years). We classified the findings of Technegas images into 4 grades. Comparing planar and SPECT images of Technegas, more detailed findings were shown by SPECT than by planar images in mild cases (6 cases, 30%). In more severe cases, findings of SPECT and planar images were equivalent (14 cases, 70%). The degree of abnormal findings obtained by SPECT was equivalent to that obtained by CT in severe cases (6 cases, 30%). SPECT should be excluded in advanced stages as indicated by planar images.

Adult↗
PubMed1997

The change of periapical exudate prostaglandin E2 levels during root canal treatment.

We have previously demonstrated that detectable levels of prostaglandin E2 exist in periapical exudates (PE-PGE2) from root canals of periapical periodontitis. Our data from a cross-sectional study also suggested the association of PE-PGE2 concentrations with the active phase of periapical lesions. The objective of this study was to investigate the longitudinal changes of PE-PGE2 levels during root canal treatment. Periapical exudate specimens were quantitatively sampled from root canals of 20 nonvital teeth at consecutive treatment visits to measure PGE2 concentrations. The mean PE-PGE2 levels significantly decreased following the endodontic therapy (158.0 +/- 54.1 pg/microliter in the first samples versus 48.4 +/- 37.9 pg/microliter in the second samples). A significant correlation was also found between the changes in PE-PGE2 levels and the clinical disease expression of periapical periodontitis (p < 0.01). Decreased PGE2 production is considered to reflect the remission of disease activity. These results suggest the central roles of PGE2 in regulatory mechanisms for the expression of periapical disease.

Dental Pulp Cavity↗
PubMed1997

A novel near infra-red spectrophotometry system using microprobes: its evaluation and application for monitoring neuronal activity in the visual cortex.

A novel near-infrared (NIR) spectrophotometry system with microprobes of optical transmitter and receivers (550 and 410 microm in diameter, respectively) has been developed. A three-dimensional profile of the signal source estimated in in vitro experiments showed two spindle-shaped regions around the respective probes, suggesting that the signal detected by the present system comes from a relatively restricted region around each probe. Next, we examined how the concentration of oxygen in inspired gas affected the NIR signals in the rat cerebral cortex in vivo. Calculated concentrations of oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb) in the rat cortex changed in mirror-image fashion in response to the change in the O2 concentration in the inspired gas. Finally, NIR responses to visual stimulation were recorded from the striate cortex of conscious adult cats that had been monocularly deprived since the peak of the sensitive period. Corresponding to the results of previous electrophysiological studies, stimulation of the normal eye induced significant NIR signals, whereas that of the deprived eye evoked no response. These results indicate that this new NIR system can be applied to study changes in oxygen metabolism in relatively restricted regions following neuronal activation in the brain.

Animals↗
PubMed1997

Influence of ETR-p1/f1 antisense peptide on endothelin-induced constriction in rat renal arcuate arteries.

1. This study set out to examine the endothelin receptor subtypes mediating vasoconstriction in the rat renal arcuate artery. This was done in isolated vessels 120-200 microns in diameter, incubated with a selective agonist and the novel 'antisense' peptide to part of the human endothelinA receptor. 2. Groups of vessels (n = 6) were incubated with increasing concentrations of endothelin-1 (ET-1), from 1 to 100 nM, which caused a 65% maximal contraction at the highest dose with an pEC50 of 8.16 +/- 0.11 M. By contrast, in six other vessels sarafotoxin 6c over the same dose range gave a minimal contraction (around 5% of maximum). 3. Preincubation of six vessels with the antisense peptide ETR p1/f1 at 1 microM had no effect on the ET-1 induced vasoconstriction, in terms of displacement of the concentration-response curve or the maximal tension achieved by the agonist. In the six vessels exposed to 4 microM ETR p1/f1, there was a significant shift of the concentration-response curve and a lower pEC50 at 7.78 +/- 0.09 M (P < 0.05). At the highest concentrations of ETR p1/f1, there was a marked suppression of all responses to ET-1, which at the maximal concentrations tested, 0.1 microM, only reached some 10% of the maximal achievable contraction. 4. Increasing ET-1 concentrations up to 2 microM in vessels incubated with 40 microM ETR-p1/f1 showed that the blockade could be overcome and that the relationship was shifted to the right (P < 0.001) by approximately one log unit with a pEC50 of 7.13 +/- 0.11 M. A Schild plot of the data indicated the antagonist to be acting competitively at a single population of receptors. 5. At the highest concentrations tested, 40 microM, ETR-p1/f1 had no effect on noradrenaline-induced contractions, indicating a lack of non-specific actions. 6. Together, these data suggest that at the rat renal arcuate artery the endothelinA receptor is the predominant functional receptor mediating contraction. Furthermore, this study has shown the potential usefulness of this novel type of 'antisense' peptide in blocking receptor activation.

Amino Acid Sequence↗
PubMed1997

The serum resistance of malaria-infected erythrocytes.

IgG and IgM antibodies were detected on non-parasitized as well as parasitized erythrocytes (E) from mice surviving over 15 days after infection with rodent malaria, Plasmodium berghei, whereas C3 was detected exclusively on parasitized E. Parasitized E, however, were quite resistant to the haemolytic activity of guinea pig complement and effectively inactivated human C3b to iC3b on their surface. Similarly, parasitized E were extremely resistant to homologous complement as assessed by haemolysis and C3 binding even when regulatory proteins (decay-accelerating factor, DAF; complement receptor related gene y, Crry; heat-stable antigen, HSA) were blocked with specific antibodies. DAF and Crry were equally expressed on both normal E and parasitized E from mice within a week post-infection; therefore, molecules that inhibit the haemolysis or C3 binding of parasitized E appear to be independent of DAF and Crry. Unexpectedly, the molecular forms of HSA and DAF in parasitized erythrocyte membranes were found to be different from those of normal erythrocyte membranes: DAF was detected as three bands (85,000, 64,000 and 30,000 MW) by immunoblotting. HSA was detected as more highly glycosylated forms than normal HSA. These alterations of DAF and HSA could be explained by the modification of membrane proteins and polysaccharides induced by parasitization, and we hypothesize that these changes of membranes or membrane proteins are involved in the resistance of parasitized E against homologous complement.

Animals↗
PubMed1997

Pitfalls of measuring residual urine volume in orthotopic neobladders.

OBJECTIVE: To investigate the pitfalls of measuring postvoid residual urine volume (PVR) in patients with orthotopic neobladders, in an out-patient clinic. PATIENTS AND METHODS: Fifteen patients with orthotopic neobladders were enrolled in the study; five patients had a colonic neobladder, five an ileocolic neobladder and five a sigmoid neobladder. The PVR was compared after measuring by catheterization under fluoroscopic monitoring after normal or forced voiding. RESULTS: The PVR after forced voiding was always less than that after natural voiding, regardless of the type of neobladder. CONCLUSIONS: Patients with orthotopic neobladders may have a higher PVR after voiding naturally at home than when the PVR measured in hospital.

Aged↗