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Biomedical subjects

K Kikuchi

Publications and source records attributed to K Kikuchi.

At least 487 records · Page 27Linked to original sources
PubMed1996

Decreased ET(B) receptor expression in human metastatic melanoma cells.

In this study, we examined the endothelin (ET) receptor subtype involved in mitogenic signaling in human primary and metastatic melanoma cell lines. In a reverse transcriptase-polymerase chain reaction (RT-PCR) study, ET(B) mRNA expression in metastatic melanoma cells was decreased from that of primary melanoma. Only RPM-EP, a primary recurrent melanoma cell line, showed strong ET(A) mRNA expression. ET-1 and ET-3 stimulated DNA synthesis of primary and recurrent cutaneous melanoma cells in serum-deprived cultures. The growth response to ET-1 in metastatic melanoma cells was decreased from that in primary melanoma cells. [125I]-IRL-1620 binding to PM-WK, a primary melanoma cell line, was significantly blocked by excessive amounts of unlabeled BQ-788. [125I]-IRL-1620 binding to metastatic melanoma cells was significantly decreased from that of primary melanoma cells. From these results, we conclude that the mitogenic effects of ET in human primary melanoma are mainly mediated through ET(B) receptors and that down-regulation of ET(B) receptors causes the decreased growth response of ET-1 in metastatic melanoma cells.

Amino Acid Sequence↗
PubMed1996

Molecular cloning of a novel cytoplasmic protein tyrosine phosphatase PTP epsilon.

We have isolated a cDNA of a novel cytoplasmic variant of the protein tyrosine phosphatase epsilon (PTP epsilon) from rat spleen cDNA library. Its deduced amino acid sequence of 642 residues was 94.6% identical to C-terminal 642 residues of human PTP epsilon (HPTP epsilon). However, N-terminal 12 amino acid residues of the rat PTP epsilon had no homology to HPTP epsilon. The unique N-terminal sequence of the rat PTP epsilon was shorter and much more hydrophilic than the transmembrane domain of HPTP epsilon. These results strongly suggest that the rat PTP epsilon, designated here as PTP epsilon C, is a novel cytoplasmic PTP with two tandem catalytic domains. We also isolated by RT-PCR a rat transmembrane PTP epsilon cDNA, designated as PTP epsilon M, which has the extracellular and transmembrane domains in addition to the common sequence to the PTP epsilon C. These results suggested that the PTP epsilon C and PTP epsilon M are generated from a single gene and may be involved in multiple functions in signal transduction.

Alternative Splicing↗
PubMed1996

Insulin-like growth factor-II as a prognostic factor in pulmonary adenocarcinoma.

We stained resected specimens from 117 patients with pulmonary adenocarcinoma for insulin-like growth factor-II (IGF-II) by the avidin-biotin-peroxidase (ABC) method and evaluated the usefulness of IGF-II as a prognostic factor. The patients were classified into the IGF-II (+) groups showing staining of 1% or more cancer cells (60 patients) and the IGF-II (-) groups showing staining of <1% (57 patients). The 5-year survival rate was 22% in the IGF-II (+) group and 54% in the IGF-II (-) group (P<0.01). Our results suggest the usefulness of IGF-II stainability as a prognostic factor of pulmonary adenocarcinoma.

Adenocarcinoma↗
PubMed1996

Fas-mediated apoptosis is modulated by intracellular glutathione in human T cells.

Fas antigen is a member of the tumor necrosis factor receptor family that transduces a lethal signal to the Fas-sensitive cells. We previously established the Fas-resistant variant cell lines LAC2D1R and JKT2D1R from the parental Fas-sensitive cell lines, SUPT13 and Jurkat, respectively. Recently, we isolated the Fas-resistant variant CEM2D1R from CCRF-CEM. All of the variants were Fas+ but resistant to Fas-mediated apoptosis. Further biochemical analysis revealed that the intracellular glutathione (GSH) content of the Fas-resistant variants was higher than in the original cells. When the Fas-resistant variants were incubated with buthionine sulfoximine (BSO) or in GSH-free/cysteine-free medium to deplete GSH, Fas resistance was reversed. Incubation of the cells with cycloheximide also decreased intracellular GSH and reversed the Fas resistance. Furthermore, incubation of activated peripheral blood lymphocytes with BSO enhanced Fas-mediated apoptosis. When the Fas-sensitive cells were incubated with N-acetylcysteine (NAC), intracellular GSH was increased and Fas-mediated apoptosis was blocked. In contrast, Fas-resistant variants, as well as Fas-sensitive cells pre-treated with NAC remained susceptible to allogeneic lymphokine-activated killer cells, most likely due to perforin-dependent killing. The results suggest that Fas-mediated apoptosis, but not perforin-dependent killing, is modulated by intracellular GSH in human T lymphocytes.

Acetylcysteine↗
PubMed1996

Cardiovascular and respiratory responses to passive leg cycle exercise in people with spinal cord injuries.

The purpose of this study was to determine the effect of passive leg cycle exercise (PLE) on cardiovascular and respiratory responses in people with spinal cord injuries (PSCI). Eight PSCI with lesions from T8 to L1 and five control subjects (CS) performed PLE at pedalling frequencies of 20 or 40 rpm for 7 min at room temperature of about 25 degrees C. We measured, at rest and during PLE, the pulmonary ventilation (VE), oxygen uptake (VO2), cardiac output (Q), stroke volume (SV), heart rate (HR) and arterial blood pressure, as well as the skin blood flow (SBF) in the lower limb after PLE. An increase in pedalling frequency promoted an increase in VE and VO2 in both groups. Compared with the CS, the PSCI showed significantly smaller increases in VO2 (P < 0.05). The Qc was significantly elevated during PLE at 20 and 40 rpm in CS, and at 40 rpm in PSCI (P < 0.05). In CS, it resulted from increases in both SV and HR, whereas in PSCI, it was contributed to by a greater increase in SV without a rise in HR. In CS, the increase in pedalling frequency promoted the increases in SV and HR and consequently in Qc. In PSCI, however, the values remained constant irrespective of pedalling frequency. The arterial blood pressure and SBF in the lower limbs were unchanged by PLE in both groups. These results would suggest that passive leg exercise promotes venous return from the paralyzed lower limbs in PSCI.

Adult↗
PubMed1996

Induction of the HPV16 enhancer activity by Jun-B and c-Fos through cooperation of the promoter-proximal AP-1 site and the epithelial cell type--specific regulatory element in fibroblasts.

The epithelial cell type-specific enhancer of the human papillomavirus (HPV) type 16 termed the long control region (LCR) carries three AP-1 binding sites. We investigated the roles of the AP-1 sites for transactivation of the LCR by Jun-B that may be a cell type specific-transactivator for the HPVs in human fibroblasts in which expression of the endogenous Jun-B gene is low. Transient expression of Jun-B alone poorly activated transcriptional activity of the LCR. However, when combined with c-Fos, Jun-B activated the LCR. The promoter-proximal AP-1 site was required for transactivation of the LCR by Jun-B:c-Fos, but the site itself was not sufficient for the maximal response. The proposed cell type specific--regulatory element that harbors binding sites for NF1 as well as TEF-1 and PEA3 motifs, but neither other AP-1 sites nor the proximal enhancer region, could augment the transcriptional response of the promoter-proximal AP-1 site to Jun-B:c-Fos.

Cell Line↗
PubMed1996

Relationship between core temperature and skin blood flux in lower limbs during prolonged arm exercise in persons with spinal cord injury.

The purposes of the present study were to examine the response of the skin blood flux (SBF) in the paralyzed lower limbs of persons with spinal cord injury (PSCI) and to clarify the relationship between the SBF and core temperature during prolonged arm exercise. Eight male PSCI with lesions from T6 to L5 and six male control subjects (CS) participated in this study. The subjects rested for 60 min and then performed arm-cranking exercise at 20 W for 30 min at 25 degrees C. The tympanic membrane temperature (Tty) and SBF in the anterior thigh (SBFT) and in the posterior calf (SBFC) were continuously measured throughout the experiment. The SBFC did not change in either PSCI or CS during the experiment. The SBFT in four PSCI with high lesions (T6 to T12), remained unchanged during exercise. The SBFT in the other four PSCI with low lesions (T12 to L5, delta SBFT+) began to elevate markedly when the Tty exceeded a threshold temperature of 36.69 degrees C. The pattern of increase of SBFT in delta SBFT+ was similar to that in CS, although onset of the increase in SBFT was delayed and the peak of SBFT during exercise was significantly lower in comparison with the CS. We consider that these differences between the delta SBFT+ and CS were largely attributable to the lower Tty in the former group, which took a prolonged time to reach the threshold of 36.69 degrees C.

Adult↗
PubMed1996

Assignment of the gene encoding type 1 gamma protein phosphatase catalytic subunit (PPP1CC) on human, rat, and mouse chromosomes.

Using fluorescent in situ hybridization (FISH) method, a gene encoding the catalytic subunit of protein phosphatase type 1 gamma (PPP1CC) was mapped to human 12q24.1-q24.2, rat 7 q22, and mouse 10C. These results indicate that the PPP1CC is a member of conserved synteny group between rat chromosome 7, mouse chromosome 10 and human chromosome 12. These data and mapping data about other members of PP1 family show that in spite of the high identity of PP1 isoforms, each isoform is encoded by different genes which located on different chromosomes in human, rat, and mouse.

Animals↗
PubMed1996

Effect of maximal arm exercise on skin blood flux in the paralyzed lower limbs in persons with spinal cord injury.

The purpose of the present study was to examine the effect of maximal arm exercise on the skin blood circulation of the paralyzed lower limbs in persons with spinal cord injury (PSCI). Eight male PSCI with complete lesions located between T3 and L1 performed graded maximal arm-cranking exercise (MACE) to exhaustion. The skin blood flux at the thigh (SBFT) and that at the calf (SBFC) were monitored using laser-Doppler flowmeter at rest and for 15 s immediately after the MACE. The subject's mean peak oxygen uptake and peak heart rate was 1.41 +/- 0.22 l.min-1 and 171.6 +/- 19.2 beats.min-1, respectively. No PSCI showed any increase in either SBFT or SBFC after the MACE, when compared with the values at rest. These results suggest that the blood circulation of the skin in the paralyzed lower limbs in PSCI is unaffected by the MACE.

Adult↗
PubMed1996

Elevated soluble CD23 levels in the sera from patients with localized scleroderma.

Soluble CD23 (sCD23) is closely related to B-cell activation and elevated serum levels of sCD23 have been reported in several autoimmune disorders. This study investigated the serum levels of sCD23 and determined the correlation of sCD23 with other immunologic abnormalities and clinical features in localized scleroderma. We examined 49 serum samples by an enzyme-linked immunosorbent assay in the following three subgroups: 15 patients with generalized morphoea, 22 with linear scleroderma, and 12 with morphoea. The serum levels of sCD23 were significantly elevated in patients with localized scleroderma, compared with those in healthy individuals. Of the three subgroups of localized scleroderma, patients with generalized morphoea had the highest levels of serum sCD23. The frequency of IgM antihistone antibody (AHA) and IgM rheumatoid factor (RF), the number of linear lesions, and the frequency of muscle involvement were significantly higher in patients with elevated sCD23 levels than in those with normal levels of sCD23. A significant correlation between the serum sCD23 level and the number of involved areas of the body was observed. Our data suggest that the activation of virgin B cells, which is reflected by elevated sCD23 levels, is closely associated with the production of IgM autoantibodies in localized scleroderma and furthermore that the serum levels of sCD23 are a new serological indicator of the severity of localized scleroderma.

Adolescent↗
PubMed1996

Soluble CD4 and CD8 in serum from patients with localized scleroderma.

Localized scleroderma has been shown to be accompanied by various immunologic abnormalities. To obtain functional information on activated CD4+ or CD8+ T cells, we studied the levels of soluble CD4 (sCD4) and soluble CD8 (sCD8) in serum from patients with localized scleroderma. Serum samples were examined by enzyme-linked immunosorbent assay. The samples were obtained from 49 patients in the following three subgroups: 15 patients with generalized morphea, 22 with linear scleroderma, and 12 with morphea. The levels of sCD4 and sCD8 were significantly elevated in patients with generalized morphea. Furthermore, these patients showed significantly higher levels of sCD4 than those with systemic sclerosis (SSc). The frequency of positivity for IgG anti-single-stranded DNA (ssDNA) antibody was significantly higher in localized scleroderma patients with elevated sCD4 levels than in patients with normal sCD4 levels. The frequency of positivity for antinuclear antibodies, IgM antihistone antibodies, IgG anti-ssDNA antibody and rheumatoid factor, and elevated sCD23 levels were significantly higher in localized scleroderma patients with elevated sCD8 levels than in patients with normal sCD8 levels. Our findings suggest that both CD4+ and CD8+ T cells are activated in vivo in generalized morphea and that the immunologic events in generalized morphea are different from those in SSc.

Adult↗
PubMed1996

Epidermal growth factor receptor-dependent cytotoxic effect by an EGF-ribonuclease conjugate on human cancer cell lines--a trial for less immunogenic chimeric toxin.

Mammalian pancreatic ribonuclease (RNase) was conjugated chemically via a disulfide bond to human or murine epidermal growth factor (EGF). The conjugation between EGF and RNase was ascertained by SDS-PAGE using reduced and nonreduced conjugates. The EGF-RNase conjugate retained potent RNase activity and competed with 125I-EGF for binding to EGFR to the same extent as unconjugated EGF. Both the human and murine EGF-RNase conjugates showed dose-dependent cytotoxicity against EGFR-overexpressing A431 human squamous carcinoma cells with IC50 values of 3 x 10(-7) M and 6 x 10(-7) M, respectively, whereas free RNase had an IC50 of 10(-4) M. Against the EGFR-deficient small-cell lung cancer cell line H69, the EGF-RNase conjugate had no cytotoxic effect. The Human EGF-RNase conjugate showed dose-dependent cytotoxicity against other squamous carcinoma cell lines (TE-5, TE-1) and breast cancer cell lines (BT-20, SK-BR-3, MCF-7) and the cytotoxicity of the conjugate correlated positively with the level of expression of EGFR by each cell line. An unconjugated mixture of EGF and RNase had no greater effect than RNase alone on any cell line. Excess free EGF blocked EGF-RNase conjugate cytotoxicity against A431 cells. These results suggest that the EGF-RNase conjugate may be a more effective anticancer agent with less immunogenicity than coventional chimeric toxins.

Antineoplastic Agents↗
PubMed1996

The basic fibroblast growth factor and its receptor in pulmonary adenocarcinomas: an investigation of their expression as prognostic markers.

The expression of basic fibroblast growth factor (bFGF) and its receptor, the high-affinity type I basic fibroblast growth factor receptor (FGFR-1): were immunohistologically studied in tissues specimens from 167 patients with a pulmonary adenocarcinoma. Of the 167 specimens, 82 (49%) expressed bFGF and 104 (62%) expressed FGFR-1, bFGF and FGFR-1 were simultaneously expressed in 72 (43%). It was also found that many patients who showed intensely positive staining for bFGF were also positive for FGFR-1, and that the expression of bFGF or FGFR-1 or both was associated with p-stage, T and N factors. The overall prognosis was significantly poorer in the bFGF-positive or FGFR-1-positive patients than in negative patients (P < 0.01). The prognosis was also significantly poorer in all patients positive for both bFGF and FGFR-1 than in those negative for both (P < 0.01); this was also true for stage I patients (P < 0.05). Multivariate analysis showed that bFGF had a significant affect on prognosis, whereas FGFR-1 did not. As FGFR-1 is significantly linked with the bFGF expression, it may be that FGFR-1 interferes with the bFGF effect on survival. These findings suggest that bFGF and FGFR-1 play important roles in tumour progression, and that bFGF expression may be a useful prognostic marker for pulmonary adenocarcinomas.

Adenocarcinoma↗