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Biomedical subjects

H Kojima

Publications and source records attributed to H Kojima.

At least 307 records · Page 17Linked to original sources
PubMed1997

[Cortical status marmoratus in a patient with a sequela of postnatal anoxic encephalopathy].

Status marmoratus (ST) of the basal ganglia and thalamus has been observed in cases of perinatal hypoxic ischemic encephalopathy and rarely of postnatal encephalopathy. In occasional cases, the cerebral cortex is also involved. Here, we reported a 22-year-old male with a sequela of postnatal anoxic encephalopathy. He had been bedridden with severe mental retardation since he suffered anoxic encephalopathy at 3 months of age. ST was found in the cerebral cortex as well as basal ganglia and thalamus. In addition to ST, the cerebral cortex and white matter were remarkably devastated. We also performed a preliminary immunohistochemical study to investigate the process of ST formation, using antibodies against glial fibrillary acidic protein (GFAP), myelin basic protein (MBP) and synaptophysin. MBP-positive abnormal myelinated fibers were identified in the ST areas, which were not colocalized with GFAP-immunopositivity. Synaptophysin was positive in the areas of ST, which were not stained with Holzer method. These results suggest that the myelination in the early infancy damage of basal ganglia and cerebral cortex could be implicated in the formation of ST.

Adult↗
PubMed1997

[Quantitative determination of serum anti ribosomal-P protein antibody by enzyme immunoassay].

An enzyme immunoassay for serum anti-ribosomal P protein antibodies (anti-P) is developed, using highly purified synthetic ribosomal P peptides of the carboxyl terminal 22 amino acid sequence conjugated to human serum albumin (HSA) as an antigen. Anti-P levels were determined by subtracting the nonspecific binding activities to HSA. The concentration of anti-P which produced half of the maximal absorbance at 492 nm (OD492) given by saturating concentrations of anti-P in the ELISA plate was defined as 1 U/ml. The anti-P values in the samples were determined by referring to a standard curve made from a standard serum containing anti-P. Serum anti-P levels in 34 normal individuals were 5.52 +/- 8.39 U/ml (mean +/- SD). Anti-P in sera from 45 patients with systemic lupus erythematosus (SLE), 24 patients with rheumatoid arthritis (RA) and 27 patients with Behçet's disease were also analyzed. The values for serum anti-P in SLE, RA and Behçet's disease groups were 251.04 +/- 843.07 U/ml, 5.97 +/- 15.18 U/ml, and 2.62 +/- 3.35 U/ml (mean +/- SD) respectively. The positive ratio for serum anti-P in SLE patients was significantly higher than that in patients with RA or Behçet's disease (p < 0.05 as determined by chi-square test). These results indicate that quantitative determination of serum anti-P by our enzyme immunoassay is a successful tool for the diagnosis of SLE.

Adult↗
PubMed1996

Apoptosis of pregnancy-dependent mammary tumor and transplantable pregnancy-dependent mammary tumor in mice.

Pregnancy-dependent mammary tumors (PDMT) of GR/A mice and transplantable PDMT (TPDMT-4 line) in DDD mice, are exceptionally stable in hormone dependence, continue to grow until parturition and regress soon after delivery. In order to study the regression mechanism of PDMT and TPDMT-4, morphological and biochemical changes were examined in the tumors removed on day 18 (TPDMT-4) or day 20 (PDMT) of pregnancy, and on the expected parturient and the following postpartum days. DNA fragmentation occurred from day 18 (TPDMT-4) or day 20 (PDMT) of pregnancy to the day after parturition. Apoptotic cells were demonstrated by an in situ 3'-end labeling method, and the plateau of the number of apoptotic cells was observed on the parturient day in PDMT and on the day after parturition in TPDMT-4. Reverse transcriptase polymerase chain reaction showed that expression of Fas was slightly increased but that of bcl-2 was decreased during the process of involution of TPDMT-4 and PDMT. These results suggest that both an increase in expression of Fas and decrease in expression of bcl-2 are involved in the apoptosis of pregnancy-dependent mammary tumor cells after parturition.

Animals↗
PubMed1996

Cortical speech processing mechanisms while vocalizing visually presented languages.

To elucidate cortical processing during vocalization, we used positron emission tomography to measure regional cerebral blood flow during vocalization in six Japanese subjects. During reading Japanese sentences used daily or short syllables aloud, the visual cortices, the left Heschl's gyrus, Broca's area, the primary motor area of the articulatory organs, the supplementary motor area and the cerebellum were significantly activated, compared with resting conditions. The superior temporal gyri were rarely activated. Significant activation of the cerebellum was observed by comparing cortical activity during reading sentences used daily with that during reading meaningless short syllables. These results suggest that vocalization of familiar materials is taken over by the cerebellum, rather than cortical speech areas, and without engagement of the superior temporal gyri.

Adult↗
PubMed1996

SHPTP2 serves adapter protein linking between Janus kinase 2 and insulin receptor substrates.

To investigate the role of Janus kinase family (JAK1 and JAK2) in insulin signaling, we assessed their insulin-induced associations with other molecules in the cells overexpressing insulin receptors (HIRc and CHO-IR). After insulin stimulation, pp185 proteins (insulin receptor substrate, IRS) were co-immunoprecipitated with both kinases by alpha JAK1 and alpha JAK2 antibodies. However, JAK2 constitutively associated with pp95 protein (IR beta). Moreover, JAK2 also constitutively bound to a protein tyrosine phosphatase containing Src 2 regions (SHPTP2), but JAK1 did not. In HIRc cells expressing PTPase-negative mutant SHPTP2, no association of JAK2 with either pp185 or pp95 was detected. Thus, SHPTP2 might serve as an adapter protein linking between JAK2 and IRS. These results suggest that JAK1 and JAK2 behave differently and they may constitute a new regulatory component in insulin signaling.

Animals↗
PubMed1996

Activation of the CPP32 protease in apoptosis induced by 1-beta-D-arabinofuranosylcytosine and other DNA-damaging agents.

The response of human myeloid leukemia cells to treatment with 1-beta-arabinofuranosylcytosine (ara-C) includes the induction of apoptosis. Ara-C induced apoptosis is associated with proteolytic cleavage of poly(ADP-ribose) polymerase (PARP) and protein kinase C (PKC) delta. However, the signals involved in this response are unknown. The present studies show that ara-C treatment of U-937 cells is associated with induction of a protease activity that cleaves the tetrapeptides Ac-DEVD-pNA and Ac-DMOD-pNA found at the cleavage sites of PARP and PKC delta, respectively. The ara-C-induced protease activity was sensitive to overexpression of the anti-apoptotic protein Bcl-xL and the baculovirus protein p35. By contrast, overexpression of the cowpox virus protein CrmA blocked apoptosis induced by engagement of the Fas receptor but not that induced by ara-C. CrmA overexpression also had no detectable effect on ara-C-induced cleavage of PKC delta. The results further show that ara-C induces activation of the CPP32 protease by a CrmA-insensitive and p35-sensitive mechanism. Similar results were obtained with cisplatinum, etoposide, and camptothecin. These findings indicate that ara-C and other DNA-damaging agents activate a CrmA-insensitive apoptotic pathway involving CPP32 and that these signals differ from those associated with apoptosis induced by the Fas receptor.

Antimetabolites, Antineoplastic↗
PubMed1996

A novel fucosyltetrahexosylceramide in plerocercoids of the parasite Spirometra erinacei.

This glycosphingolipid was tentatively designated as GalSEGLx, in which the carbohydrate structure is characterized by an additional galactose molecule attached to the reducing-end galactose of SEGLx [Gal beta-4 (Fuc alpha-3) Glc beta-3 Gal beta Cer], which was previously determined by us [Kawakami, Y., Nakamura, K., Kojima, H., Suzuki, M., Inagaki, F., Suzuki, A., Sonoki, S., Uchida, A., Murata, Y. & Tamai, Y. (1993) J. Biochem. 114, 677-683], through a beta 1-6 linkage. The ceramide contained sphinganine and 4D-hydroxysphinganine in an about equimolar ratio, and a non-hydroxy fatty acid with carbon atoms ranging from 16 to 28, 26:0, 28:0 and 28:1 being major components. Based on the finding that a novel carbohydrate structure. Gal beta-4 Glc beta-3 Gal, was commonly found in glycosphingolipids from the parasite, S. erinacei, we here propose the terms, spirometo series, for this core structure series, and spirometosides, for glycosphingolipids having this carbohydrate structure.

Animals↗
PubMed1996

A central role for Stat3 in IL-6-induced regulation of growth and differentiation in M1 leukemia cells.

Interleukin-6 (IL-6) induces either differentiation or growth of a variety of cells. Little is known about the molecular basis of this cellular decision. The family of signal transducer and activator of transcription (Stat) proteins are involved in signaling through a variety of cytokine and growth factor receptors, although their biological roles have not been established. To address whether Stat proteins play roles in IL-6-induced growth or differentiation, we introduced two types of mutant Stat3 acting in a dominant-negative manner into M1 leukemic cells which respond to IL-6 with growth arrest and terminal differentiation. We show that dominant-negative forms of Stat3 inhibited both IL-6-induced growth arrest at G(0)/G1 and macrophage differentiation in the M1 transformants. Blocking of Stat activation resulted in inhibition of IL-6-induced repression of c-myb and c-myc. Furthermore, IL-6 enhanced the growth of M1 cells primarily through shortening the length of the G1 period when Stat3 was suppressed. Thus IL-6 generates both growth-enhancing signals and growth arrest- and differentiation-inducing signals at the same time. Stat3 may be a key molecule which determines the cellular decision from cell growth to differentiation in M1 cells.

Animals↗
PubMed1996

Synthesis and structure-activity relationships of 2-substituted D-tryptophan-containing peptidic endothelin receptor antagonists: importance of the C-2 substituent of the D-tryptophan residue for endothelin A and B receptor subtype selectivity.

Continuing studies on modifications of potent cyclic pentapeptide endothelin (ET) receptor antagonists, represented by BQ-123, and potent linear tripeptide derivative ET receptor antagonists, represented by BQ-788, are described herein. The introduction of D-tryptophan analogues with C-2 substituents in these peptidic ET antagonists resulted in potent ET receptor antagonists with various ETA/ETB subtype selectivity. Combined ETA/ETB receptor antagonists were found in both cyclic pentapeptide and linear tripeptide series with 2-halo- and 2-methyl-D-tryptophans. In contrast, compounds with 2-cyano-D-tryptophan were ETB receptor-selective antagonists. The C-2 substituent of the D-tryptophanyl residue appeared to be very important for the discrimination of ETA/ETB subtype selectivity of the antagonists. The potent ET receptor antagonists with various ETA/ETB subtype selectivity synthesized in this study may be useful tools for elucidating the physiological and pathophysiological roles of ET and ET receptors.

Animals↗
PubMed1996

Expression of human phospholipid hydroperoxide glutathione peroxidase gene for protection of host cells from lipid hydroperoxide-mediated injury.

A cDNA encoding human phospholipid hydroperoxide glutathione peroxidase (PHGPx) was obtained by PCR amplification from human testis cDNA and was inserted into the plasmid pRc/CMV to construct an expression vector for human PHGPx. Guinea pig cell line 104C1 cells were transfected with the expression vector. One of the transfectants, designated 104Cl/O4C, expressed high glutathione peroxidase activity toward dilinoleoyl phosphatidylcholine hydroperoxide and linoleic acid hydroperoxide. Western blot analysis revealed a large amount of protein immunoreactive against anti-PHGPx antibody in the transfectant. When the cells were incubated with these hydroperoxides, the parental cells suffered from serious cell injury, whereas the transfectant was extremely resistant against lipid hydroperoxide-mediated injury.

Animals↗
PubMed1996

IL-6-inducible complexes on an IL-6 response element of the junB promoter contain Stat3 and 36 kDa CRE-like site binding protein(s).

The junB gene is one of immediate-early genes whose expression are regulated by a variety of extracellular stimuli and play important roles in cellular responses to the given stimuli. Interleukin-6 (IL-6) activates the junB promoter through an IL-6 response element, JRE-IL6, that is composed of two cooperative DNA motifs, a low affinity Stat-binding site overlapping with an Ets-binding site (JEBS) and a cAMP responsive element (CRE)-like site. This element is a target for the Jak-Stat signal transduction pathway. We showed that IL-6 induced novel complexes on JRE-IL6, termed JRE-IL6-BC1 and 2, which contained Stat3 but migrated more slowly than the complexes containing homo- or heterodimer of Stat3 and Stat1 in gel shift assays. These slow-migrating JRE-IL6-BCs appeared to contain CRE-like site binding proteins besides Stat3, since the formation of JRE-IL6-BCs required both the JEBS and CRE-like site of JRE-IL6 and oligonucleotides containing the CRE-like site or somatostatin CRE efficiently competed with JRE-IL6 for making JRE-IL6-BCs. The formation of the complexes correlated well with the responsiveness of JRE-IL6 to IL-6 signals. U.v.-cross linking study revealed that JRE-IL6 bound a 90 kDa protein, corresponding to Stat3, and a 36 kDa protein, most likely a CRE-like site binding protein(s). Furthermore, we showed that the IL-6/interferon gamma (IFN gamma) response element in the IRF-1 promoter (IR/IRF-1), which contains a Stat-binding site and an adjacent CRE-like site, also makes IL-6-induced binding complexes similar to JRE-IL6-BCs.

Base Sequence↗
PubMed1996

Expression of messenger RNA for keratinocyte growth factor in human cholesteatoma.

OBJECTIVE: To understand the interaction between cholesteatoma epithelium and subepithelial connective tissue as a paracrine regulation by keratinocyte growth factor. DESIGN: Preparation of a specific DNA probe from human fetal fibroblast and detection of localization of keratinocyte growth factor messenger RNA in subepithelial granulation tissue of middle-ear cholesteatoma by a nonradioactive in situ hybridization method. PARTICIPANTS: The cholesteatoma specimens were excised from 12 patients during surgery. Normal skin specimens collected from the external ear canal of six patients were used as controls. RESULTS: Signals specific for keratinocyte growth factor messenger RNA were not expressed in the normal skin of the external ear canal, but were observed in fibroblasts of subepithelial connective tissue of cholesteatoma specimens. Signals were observed only in specimens collected from patients whose subepithelial connective tissue was thick and proliferated and whose inflammation was strong. CONCLUSIONS: A paracrine regulation mechanism involving keratinocyte growth factor may exist for proliferation of epithelium of cholesteatoma. The subepithelial connective tissue of cholesteatoma may play an important role in the proliferation and development of the cholesteatoma, especially under inflammatory conditions.

Base Sequence↗
PubMed1996

Ultrastructural localization of adhalin in normal murine skeletal myofiber.

The ultrastructural localization of adhalin and its relations to dystrophin, beta-dystroglycan, and beta-spectrin were studied in normal murine skeletal myofibers. The C-terminal peptides of adhalin and beta-dystroglycan were synthesized based on their cDNAs, and the affinity-purified antibodies against these peptides were produced. Single-immunolabeling electron microscopy showed that the adhalin was located just inside the muscle plasma membrane or inside the myofiber a short distance from the plasma membrane. The adhalin signal was also noted at the sarcoplasmic side of plasmalemmal invaginations or at vesicular structures in subsarcolemmal areas. Double-immunogold-labeling electron microscopy disclosed a similar localization of dystrophin, beta-dystroglycan, and beta-spectrin. The close association of adhalin with dystrophin or beta-dystroglycan was demonstrated by formation of doublets by signals of antibodies of adhalin with those of dystrophin or beta-dystroglycan and was confirmed by statistical analyses. This study demonstrated that the location of adhalin is close to that of dystrophin and beta-dystroglycan at the muscle plasma membrane.

Animals↗
PubMed1996

The effectiveness of medroxyprogesterone in the treatment of multiple metastasizing leiomyosarcomas: report of a case.

A 51-year-old woman was admitted to our hospital for further investigation of chest X-ray films which showed multiple shadows that had been growing slowly over 2 years. Her only symptom was hemosputa. The lesions were suspected of being metastasizing leiomyoma due to her past history of uterine leiomyoma. Just 1 week before undergoing scheduled open lung biopsy, the lung lesions increased remarkably in size and number. A thoracotomy was performed and six of the numerous nodules were removed. The resected specimens were pathologically diagnosed as metastasizing leimyosarcoma which was positive for the progesterone and estrogen receptors. Thus, 1 month postoperatively, a course of medroxyprogesterone (MPA), 600 mg daily, was commenced. The residual lesions in her chest started to diminish, shortly afterward. She has remained well on this MPA regimen for 45 months. The prognosis of patients with metastasizing leiomyosarcoma is poor because of its low sensitivity to chemotherapy; however, some types of leiomyosarcoma are hormone-sensitive. It is therefore important to examine the hormone receptors of excised tumors from patients suspected of having metastasizing leiomyoma or leimyosarcoma.

Antineoplastic Agents, Hormonal↗
PubMed1996

Biosynthesis of a blood group H1 antigen by alpha 1, 2-fucosyltransferase in PC12 cells.

We have examined the expression of GDP-fucose: glycosphingolipid fucosyltransferase activity in PC12 cells and PC12 sublines in relation to the neuronal differentiation induced by nerve growth factor (NGF) or dexamethasone. Transfer of fucose to paragloboside (nLc4Cer) yielded a product which was determined to be a blood group H1 antigen (Fuc alpha 1-2Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc-Cer) by gas chromatography/mass spectrometry analysis and enzymatic hydrolysis, suggesting that PC12 cells have an alpha 1,2-fucosyltransferase. Lactosylceramide was also fucosylated at a reduced rate. When the differentiation of PC12 cells and PC12 subline cells, PC12D and MR31, was induced by exposure to either NGF or dexamethasone, the fucosyltransferase activity for nLc4Cer was found to decrease in both cell lines, suggesting the association with cell differentiation. This is the first report of the presence of an alpha 1,2-fucosyltransferase in cultured neuronal cell lines which catalyses the in vitro biosynthesis from nLc4Cer of a type-2 chain glycosphingolipid having the blood group H1 determinant. The disaccharides, beta-lactose and N-acetyllactosamine, were also fucosylated by PC12 cell enzyme, although the specificity for the carbohydrate structure was different from that for glycosphingolipids.

ABO Blood-Group System↗
PubMed1996

Electron microscopic observations of triple immunogold labelling for dystrophin, beta-dystroglycan and adhalin in human skeletal myofibers.

Dystrophin is the Duchenne muscular dystrophy gene product and is a membrane cytoskeletal protein present in the network of the plasma membrane undercoat. Adhalin (50 kDa dystrophin-associated glycoprotein) and beta-dystroglycan (43 kDa dystrophin-associated glycoprotein) are the transmembrane components of the normal muscle plasma membrane, and beta-dystroglycan has been demonstrated to bind dystrophin at the inside surface of normal muscle plasma membrane. This investigation was undertaken to test whether the epitopes of dystrophin, beta-dystroglycan and adhalin are closely associated with each other by using triple immunogold labelling electron microscopy on normal human skeletal myofibers. Although closely associated signals of triplet immunogold particles were observed, there were less numerous than expected. However, closely associated signals of two epitopes of dystrophin and beta-dystroglycan, dystrophin and adhalin, or adhalin and beta-dystroglycan were frequently observed. These ultrastructural findings are consistent with biochemical evidence implying that dystrophin, beta-dystroglycan and adhalin are closely associated with each other at the normal muscle plasma membrane.

Cytoskeletal Proteins↗