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Biomedical subjects

H Abe

Publications and source records attributed to H Abe.

At least 487 records · Page 27Linked to original sources

Itk, a T cell-specific tyrosine kinase, is required for CD2-mediated interleukin-2 promoter activation in the human T cell line Jurkat.

We investigated the functional role of Itk, a member of the cytoplasmic tyrosine kinase Tec family, in T cell activation. Stimulation of either CD2 or T cell receptor (TCR)/CD3 on Tcells by monoclonal antibody-mediated cross-linking induced tyrosine phosphorylation of Itk, which was maximal as early as 1 min after stimulation. The tyrosine kinase activity in the anti-Itk immunoprecipitate was significantly activated upon these stimulations. Interleukin-2 (IL-2) promoter activity stimulated by cross-linking of CD2, TCR/CD3, and CD28 with antibodies was significantly reduced by transient expression of an Itk mutant lacking the kinase activity. The reduction paralleled a decrease in tyrosine phosphorylation of endogenous wild-type Itk. Stimulation of CD2 or TCR/CD3 induced activation of the nuclear factor of activated T cells (NFAT), the binding site of which is included in the IL-2 gene promoter. The activation of NFAT was also impaired by expression of the Itk mutant. These results demonstrate that Itk plays a role in IL-2 production, indicating a critical involvement of Itk in the initial stage of T cell activation by mediating signals from the TCR/CD3 complex, CD2, and CD28.

CD2 Antigens↗

[Single stage excision for an intractable brain abscess and free rectus abdominis flap for reconstruction of the anterior skull base].

A case is presented of the frontal brain abscess following resection of squamous cell carcinoma of the maxillary sinus who had undergone reconstruction of the anterior skull base using a free rectus abdominis muscle flap. Local flap, ex. galeal flap, can be used for separating the cranial space from the paranasal sinuses and the nasopharynx, but it cannot provide reliable separation and protection of the brain from bacterial flora of the upper airway and it is too weak to support the brain in cases where orbital exenteration has been performed. The distant flaps such as the pectoralis major musculocutaneous flap, on the other hand, can provide a good alternative for reconstruction of the anterior skull base in such difficult cases, but frequently requires a secondary division of the pedicle. The free flap can circumvent such problems. We used the free rectus abdominis muscle flap and the postoperative course was uneventful. A bone graft was not necessary to reconstruct the anterior skull base.

Brain Abscess↗

Potentiation of the antitumor activity by a novel quinoline compound, MS-209, in multidrug-resistant solid tumor cell lines.

A novel quinoline compound, MS-209, was examined for its ability to reverse multidrug resistance (MDR) in several murine and human MDR solid tumor cell lines both in vitro and in vivo. MS-209 strongly reversed drug resistance to adriamycin (ADM) and vincristine (VCR) in acquired MDR tumor cell lines, 2780AD and KB-C1. In addition, MS-209 enhanced the cytotoxic effect of ADM and VCR on various human and murine cell lines. Particularly in 4-1St cells, which are extremely resistant to ADM and VCR, MS-209 at a concentration of 3 microM enhanced the cytotoxicity of ADM and VCR, 88- and 350-fold, respectively. MS-209 administered orally, together with ADM, enhanced the antitumor activity of ADM on Colon 26 and 4-1St tumors implanted subcutaneously (SC) in mice; the antitumor effect of ADM plus MS-209 was higher than that of ADM alone at the maximum tolerated dose (MTD). Furthermore, the coadministration schedules of MS-209 to attain the highest potentiation of ADM activity were examined using Colon 26 tumors. The maximum antitumor activity was obtained when MS-209 was administered on the same day as ADM. MS-209 administered a day before the ADM injection exhibited no potentiation effect, whereas MS-209 administered a day after the ADM injection showed a moderate effect. The effect of MS-209 was weaker when administered in a fractionated manner than when administered as a single dose. The results presented in this article suggest that MS-209 is an effective agent to overcome MDR in cancer chemotherapy.

Adenocarcinoma↗

[Magnetic resonance axonography by diffusion weighted echo planar imaging].

Anisotropy of apparent diffusivities of water molecules is known to be an excellent means for elucidating detailed information regarding neuronal fiber direction and density in live subjects. The recent development of magnetic resonance axonography (MRX) utilizing three dimensional anisotropy contrast(3DAC), using Echo Planar Imaging(EPI), a new algorithm for the treatment of apparent diffusion tensor, has provided an unprecedented opportunity for visualizing anatomic detail of the human brain. In this study, we applied the 3DAC method in normal human brain. The results clearly demonstrated that 3DAC is highly sensitive to orientation of fiber tracts. Considering the rather simple implementational process and high anatomic resolution, MRX based on the 3DAC method appears to be the ideal non-invasive imaging technique for assessment of the human brain in biomedicine.

Algorithms↗

[Parapapillary chorioretinal atrophy and parapapillary avascular area in glaucoma].

We measured the area of parapapillary chorioretinal atrophy (PPA), i.e. zone alpha and zone beta in fluorescein angiography, and parapapillary avascular area (PPAVA) in indocyanine green angiography, using scanning laser ophthalmoscope in a total of 66 eyes of 39 patients. There were 26 eyes of 16 patients with normal tension glaucoma (NTG) and 40 eyes of 23 patients with primary open angle glaucoma (POAG). Although there was no significant correlation between the areas of PPAVA, PPA, zone alpha or zone beta, and mean deviation of Humphrey field analysis, there was significant correlation between all areas except for zone alpha and the spherical equivalent. The areas of PPAVA and zone beta in the NTG group were significantly larger than those in the POAG group (p = 0.04434, 0.02750, respectively). These results suggest that the pathogenesis of disease may be different in NTG and POAG.

Adult↗

[Plateau iris configuration as a risk factor for malignant glaucoma].

To provide evidence for diagnosing malignant glaucoma, as well as to elucidate the pathogenetic mechanism of the disease, ultrasound biomicroscopy (UBM) is a useful tool. We examined the anterior segments of three patients with post-operative malignant glaucoma with UBM regarding the state before operation, the state of the opposite eye, and the state after the release of the cilio-lenticular block. Case 1 was a 76-year-old female who was diagnosed as having chronic angle-closure glaucoma (CACG) and was treated by trabeculectomy, phacoemulsification, aspiration (PEA), and simultaneous intraocular lens (IOL) implantation. Case 2 was a 22-year-old male diagnosed as having CACG secondary to plateau iris syndrome and was treated by trabeculectomy. Case 3 was a 73-year-old female diagnosed as having normal-tension glaucoma with narrow angle and was treated by PEA and IOL implantation. Slit-like anterior chamber angle and anteriorly positioned ciliary body were observed in all 3 cases, which were identical to those Pavlin reported in 8 cases with plateau iris syndrome. UBM seems to be an important pre-operative examination to evaluate the risk of malignant glaucoma and to consider which surgical procedure and post-operative management is proper. The pre-operative configuration of the ciliary body may be associated with the onset of malignant glaucoma in some patients with CACG or narrow angle.

Adult↗

Expression of cathepsin D and B in invasion and metastasis of squamous cell carcinoma.

To determine the involvement of proteinases with hydrolytic activity towards extracellular matrix and basement membrane, in invasion and metastasis of tumour cells, the expression of cathepsin D, an aspartic proteinase, and cathepsin B, a cysteine proteinase, was studied. Formalin-fixed paraffin-embedded specimens from 13 patients who had squamous cell carcinomas (SCC) with local recurrence, skin and/or lymph node metastasis were examined. Cathepsin D stained intensely as a granular pattern (mature enzyme) in tumour cells of 69% of primary lesions and all the secondary lesions of the patients with SCC. Cathepsin B stained more intensely in SCC cells of all of the primary and secondary lesions than in normal epidermis; staining patterns were almost diffuse (procathepsin B). Granular and diffuse patterns (mature enzyme of cathepsin D and procathepsin B, respectively) appeared in the outer and inner parts of tumour islands, respectively. The presence of the active mature form of cathepsin D and procathepsin B in metastatic skin lesions of SCC was confirmed by Western blotting analysis. The presence and localization of the active mature form of cathepsin D suggests that activated cathepsin D may be involved in the invasion and metastasis of SCC.

Blotting, Western↗

Functional magnetic resonance imaging of visual function in postpapilledema optic atrophy.

We studied a girl with intraventricular brain tumor who developed postpapilledema optic atrophy and severe concentric visual field constriction in both eyes. The patient had mild symptoms despite severe visual field loss. We performed functional magnetic resonance imaging using two kinds of visual stimulation to assess her residual visual function. The functional magnetic resonance imaging demonstrated that the activity in her association visual cortex was largely intact bilaterally, although the activation of the calcarine cortex was decreased in the left calcarine cortex. Her activity in the visual cortex seemed to correspond well to her visual symptom. Functional magnetic resonance imaging may be useful in objectively documenting residual visual function in patients with severe visual loss.

Adolescent↗

[Regional difference in the etiology of liver cirrhosis in Iwate].

To assess regional differences in the etiology of liver cirrhosis in Iwate, we analyzed 324 patients with liver cirrhosis treated at various hospitals. The etiology was HCV 44.8%, HBV 11.1%, HBV + HCV 4.6%, alcohol 27.5% (including heavy drinkers 17.9%), PBC 1.5% and non-B non-C 10.5% in Iwate. The incidence of alcoholic cirrhosis was higher than that in other prefectures, while that of HCV was lower. Especially in the northern area of Iwate, the rate of alcoholic cirrhosis was very high (39.1%--including heavy drinkers 21.8%) while viral cirrhosis was relatively low. Although the alcohol consumption volume in Iwate was not very high, marked alcohol consumption, especially shochu, was observed in the northern area of Iwate. The volume and kind of alcohol consumed in each area differed, and the etiology of liver cirrhosis differed regionally in Iwate. Thus, we should consider these districts and levels of alcohol consumption when treating patients with liver cirrhosis.

Female↗

Receptor protein tyrosine kinase DDR is up-regulated by p53 protein.

We have previously reported on radiation-induction of ptk-3 in rat astrocyte culture [Sakuma et al. (1995) Radiat. Res. 143, 1-7]. Ptk-3 was considered to be a rat version of human DDR (discoidin domain receptor). We cloned and analyzed genomic DNA of the DDR and its promoter region. We discovered that the promoter region contained a consensus sequence of the p53 tumor suppressor binding site. Adenovirus-mediated p53 transfection induced a high level of DDR mRNA in SAOS2 human osteosarcoma cells. These results indicate that DDR is up-regulated by the p53 protein.

Blotting, Northern↗

Properties of poly(ADP-ribose) glycohydrolase purified from pig testis nuclei.

A poly(ADP-ribose) glycohydrolase was purified more than 5,000-fold to apparent homogeneity from pig testis nuclei with a yield of 16%. A protein band, whose molecular mass (Mr) was estimated to be 58,000, detected by SDS-polyacrylamide gel electrophoresis of the purified preparation, was shown to have glycohydrolase activity upon assay by the renaturation method. A native Mr of 51,000 was determined by gel permeation. This polypeptide is a basic protein with a pI value of 8.8. The mode of hydrolysis of poly(ADP-ribose) [(ADP-ribose)n] by this enzyme is exoglycosidic, yielding ADP-ribose as the final product. The Km value for (ADP-ribose)n (average chain length, n = 15) is 5.4 microM and the Vmax of its hydrolysis is 34.5 micromol x min(-1) x mg protein(-1). The optimum pH for enzyme activity is 7.2. Low concentrations (50 approximately 150 mM) of monovalent salts stimulate the enzyme activity. The poly(ADP-ribose) glycohydrolase present in pig testis nuclei has some properties different from either nuclear poly(ADP-ribose) glycohydrolase (type I) or cytoplasmic poly(ADP-ribose) glycohydrolase (type II), purified previously from several tissues including pig thymus, guinea pig liver, calf thymus, human erythrocytes, and placenta. These differences suggest the tissue specificity of poly(ADP-ribose) glycohydrolase.

Animals↗

Leptin induces tyrosine phosphorylation of cellular proteins including STAT-1 in human renal adenocarcinoma cells, ACHN.

Several lines of evidence from in vivo animal experiments and human studies suggest that leptin, a peptide secreted from adipose tissue, plays a role in regulating food intake and energy expenditure. However, the signal transduction mechanism of leptin in its target cells remains unknown thus far since leptin-responsive cell lines have not been available yet. We found that leptin caused the tyrosine phosphorylation of several proteins in human renal cell carcinoma cells, ACHN cells, in which STAT-1, but neither STAT-3 nor STAT-5, was involved. An ACHN cell line would serve as a useful tool for analyzing the signal transduction mechanism of leptin.

Adenocarcinoma↗

Okadaic acid suppresses neural differentiation-dependent expression of the neurofilament-L gene in P19 embryonal carcinoma cells by post-transcriptional modification.

Mouse P19 embryonal carcinoma cells in aggregation culture in the presence of 10(-6) M retinoic acid followed by monolayer culture differentiate into nerve and glial cells. In this study, we demonstrated that the neurofilament-L (NF-L) mRNA and protein levels of these cells were enhanced in accordance with their retinoic acid-induced neural differentiation. Okadaic acid (OA) treatment of the cells markedly suppressed this differentiation-dependent NF-L gene expression increase and neurite outgrowth of the cells. Similar results were obtained when tautomycin was used instead of OA, suggesting that inhibition of protein phosphatase(s) is involved in the suppression of neural differentiation. OA treatment did not affect the NF-L gene transcription level, determined by the nuclear run-on transcription assay, but it did reduce the stability of both the 3.5- and 2.3-kilobase NF-L mRNAs. The expression and activity levels of protein phosphatase 2A (PP2A) and 2B (PP2B) but not protein phosphatase 1 (PP1) in P19 cells increased in accordance with the enhanced NF-L gene expression. The presence of OA in the culture medium during the course of the neural differentiation caused a reduced PP2A activity but not PP1 and PP2B activities of the cell extracts. On the other hand, both PP1 and PP2B activities but not PP2A activity of cell extracts were suppressed by the addition of cyclosporin A or FK506 in the culture medium. However, both cyclosporin A and FK506 treatments affected neither NF-L gene expression nor neurite outgrowth. These results demonstrate that the OA treatment inhibits the differentiation-dependent increase in NF-L gene expression by destabilizing its mRNAs and suggest that PP2A plays key roles in the differentiation-dependent enhanced expression of the NF-L gene and is the point of the action of OA.

Animals↗