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Biomedical subjects

S Kubota

Publications and source records attributed to S Kubota.

At least 19 recordsLinked to original sources
PubMed1992

Synergistic antiproliferative activity of human fibroblast interferon in combination with alpha-difluoromethylornithine against human gastric cancer cells in vitro.

The author has studied the effects of alpha-difluoromethylornithine (alpha DFMO), an enzyme-activated irreversible inhibitor of ornithine decarboxylase; human fibroblast interferon (IFN beta); and their combination on human gastric cancer cell growth in vitro. alpha DFMO (from 0.1 to 4 mmol/l) inhibited cell growth in a dose-dependent manner. Both alpha DFMO (0.1 mmol/l) and higher doses of IFN beta (100 and 1000 IU/ml) caused only limited inhibition of cell growth. When alpha DFMO (0.1 mmol/l) was administered in combination with IFN beta (100 and 1000 IU/ml), synergistic antiproliferative activity was observed 7 days after continuous exposure. Although the mechanisms by which this effect occurs are unclear, it appears to be associated with direct inhibition of tumor cell proliferation, possibly by modulation of polyamine metabolism.

Adenocarcinoma↗
PubMed1992

Signaling site of laminin with mitogenic activity.

Laminin, a basement membrane glycoprotein, has diverse biological activities including cell adhesion, growth, and differentiation. However, little is known concerning the signal transduction and active site involved in cell growth. In this study, we have shown that laminin and a 19-mer peptide (PA22-2) from the carboxyl-terminal end of the long arm of the laminin A chain, which was previously shown to promote cell adhesion and neurite outgrowth, stimulate thymidine incorporation and cell growth of PC12 cells. Laminin and PA22-2 (PA) were also found to induce a rapid and transient mRNA expression of c-fos and c-jun protooncogenes in PC12 cells. Further, both laminin and PA stimulated the DNA binding activity of c-Fos and c-Jun protein complex to the AP-1 site. We have also found that there is a correlation between cell growth, c-fos expression, and the ability of cell attachment to laminin or to PA in different cell types. These results suggest that the PA sequence is a potent site in laminin for both signal transduction and cell growth.

Amino Acid Sequence↗
PubMed1992

Inhibition of human immunodeficiency virus type 1 Rev function by a Rev mutant which interferes with nuclear/nucleolar localization of Rev.

A nonfunctional mutant of human immunodeficiency virus type 1 Rev was created by deleting seven amino acid residues within the nucleolar targeting signal. This mutant Rev remained in the cytoplasm in expressed cells and strongly inhibited the function of Rev by interfering with the nuclear/nucleolar localization of coexpressed Rev. These findings strongly suggest the multimerization of Rev in the cytoplasm before migration to the nucleus/nucleolus, where wild-type Rev functions as a trans-regulator.

Amino Acid Sequence↗
PubMed1992

Germ line-restricted supernumerary (B) chromosomes in Eptatretus okinoseanus.

Cytogenetic studies were performed on two types of Japanese hagfish (Eptatretus okinoseanus) that eliminate about 45% (type A) and 55% (type B) of their DNA from presumptive somatic cells during the differentiation of somatic cells. The observations revealed inter- and intraindividual variations in the number of chromosomes in germ cells of both types of hagfishes. Although the modal number of chromosomes in the germ cells was 54 in both types, the percentage of cells with the modal number was rather low (38.6% [51/132] in five specimens of type A and 22.7% [25/110] in eight specimens of type B). In addition, one of seven type B specimens clearly had a modal number of 62 chromosomes. Another specimen of type B had a bimodal distribution of chromosome numbers, with peaks of 54 and 59 chromosomes. The observation of interindividual variations was supported by data on the amount of DNA in germ cells of type B specimens. However, these variations were rarely observed in somatic cells. These results suggest that supernumerary (B) chromosomes are maintained in germ cells and are eliminated together with some other chromosomes and/or chromatin from somatic cells.

Aneuploidy↗
PubMed1992

[Person-centered approach in occupational mental health: theory, research and practice].

The objective of this study was to articulate the person-centered approach (PCAp) in theory and in the research and practice of occupational mental health. First, Carl Rogers' person-centered theory was reviewed. Secondly, a study on 1,661 workers was presented in which psychological variables such as fatigue (FG), depression (DP) and anxiety (AX) were found to be negatively correlated with relationship scales concerning the workers' perception of the person-centered attitudes (PCA) of their superiors, the democratic leadership of their superiors (DEM) and the overall activation (ACT) of their worksites. Significant differences in FG, DP and AX were found among workers who perceived of their superiors as having either high or low PCA. Workers who reported that their superiors had high PCA had significantly less FG, DP and AX than those who perceived of their superiors as having low PCA. Similar results were also obtained when high DEM/low DEM and high ACT/low ACT were compared in terms of workers' FG, DP and AX. Thus, the PCA of job superiors was considered to be positively related to the mental health of workers. Thirdly, PCA training in industry was introduced and evaluated. A total of 137 trainees (managers) conducted active listening, a basic skill in the PCAp, and filled out a relationship inventory immediately afterwards, evaluating themselves as listeners and their partners as listeners. A comparison of scores between the first and last sessions of training showed significant increases in empathy, congruence and unconditional positive regard at the last session in both the speakers' version and the listeners' version of the relationship inventory. Cases showing changes in human relations at work as a consequence of PCA training, reported by the trainees and confirmed by an occupational health nurse, were presented. This study showed that PCA, which is positively related to workers' mental health, can increase as a result of training. The implications of these studies are discussed and various possibilities for further research using the concepts of PCAp are presented. The authors hope that such a viewpoint in occupational mental health may lead to fruitful research and practice in the field of occupational medicine.

Adult↗
PubMed1992

[Lysis of autologous tumor cells by peripheral blood lymphocytes treated with IFN-alpha in patients with renal cell carcinoma].

Immunotherapy, consisting mainly of interferon (IFN) therapy, has been used to treat renal cell carcinoma refractory to radiotherapy and chemotherapy ever since IFN was reported to be effective against renal cell carcinoma in 1982. The efficacy of IFN is low, with the response rate being only about 20% and the method and duration of its administration have yet to be established. Using viable tumor cells obtained at nephrectomy, we discovered that IFN-alpha induced killer cells have a cytocidal effect on autologous renal cell carcinoma cells and that assaying the cellular immunity of the peripheral blood lymphocytes of 25 patients with renal cell carcinoma, using ACHN derived from human renal cell carcinoma as the target cells, is useful as a monitoring method during IFN-alpha therapy. Augmentation of the cytotoxicity of peripheral blood lymphocytes in response to administration of IFN-alpha was observed in all 25 cases. Cytotoxicity was activated to 5-426 LU compared with the control value of 1 LU or less before IFN therapy, when autologous renal cell carcinoma cells were used as the target cells. Cytotoxicity for ACHN cells in the control value before IFN-alpha therapy and 4 weeks after the institution of IFN-alpha administration and autologous tumor lysis in the induction assay were more strongly correlated than in the case of K562 cells. A strong correlation was also found between cytotoxicity for ACHN cells in the induction assay and 4 weeks after the institution of IFN-alpha administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[A new method of in vitro chemosensitivity test using multicellular spheroids of cholangiocarcinoma cell line cocultured with fibroblasts].

We applied the multicellular spheroids which consist of cholangiocarcinoma cell line (MEC) and human dermal fibroblasts (HDF) to in vitro chemosensitivity test. Five-day multicellular spheroids were incubated with 1.5 micrograms/ml of mitomycin C (MMC) for 24 hrs. Then, cell kinetics of MEC and HDF in a spheroid was determined by flow cytometric analysis. Twenty four hrs after treatment with MMC, both MEC and HDF were accumulated on S phase. Seven-day after treatment, DNA histogram in MEC returned to normal, but that of HDF was disappeared. These results showed that the multicellular assay could be more like on in vivo like chemosensitivity test.

Adenocarcinoma↗
PubMed1992

[Percutaneous Bacillus Calmette-Guerin perfusion of the upper urinary tract for carcinoma in situ].

We performed percutaneous perfusion of the upper urinary tract with Bacillus Calmette-Guerin (BCG) in 3 patients. Two of them had undergone unilateral nephrectoureterectomy for ureter carcinoma in situ and one had undergone radical cystectomy with bilateral ureterocutaneostomy for invasive bladder carcinoma. However, they suffered recurrent upper urinary tract carcinoma in situ within 2 years after their operation. Under ultrasound control a percutaneous nephrostomy tube was placed in the patient. Before BCG perfusion unobstructed flow from the renal pelvis to the bladder was confirmed and pyelovenous or pyelolymphatic back flow was excluded under fluoroscopy. A dose of 240 mg BCG was dissolved in 150 ml 0.9% saline. The flask was placed 20 cm above the kidney of the resting patient. A continuous flow of approximately 1 ml per minute was maintained. The perfusion was stopped after 2 hours and the nephrostomy tube was closed. Therapy was repeated at weekly intervals for a total of 6 perfusions (1 treatment course). In each of them urine cytology results became negative after 1 treatment course. No severe side effects were observed. Further investigation is also needed to determine whether BCG perfusion of the upper urinary tract could become a conservative treatment for carcinoma in situ of the upper urinary tract.

Adult↗
PubMed1992

[An evaluation of temporary clipping during aneurysmal surgery: a retrospective study].

A temporary clipping of a parent artery has been found convenient in facilitating an aneurysmal dissection. This is because it controls the bleeding from an unexpected rupture and keeps the sac collapsed during the operation. Such a temporary arterial occlusion, however, involves the risk of a focal ischemia that may lead to permanent postoperative neurological deficits. Therefore, to evaluate the influence of a temporary clipping on the outcome of an operation, a retrospective study of 302 patients who underwent an operation for a ruptured supratentorial aneurysm between 1981 and 1990 has been conducted. This study has revealed the information that follows: 1) Overall outcomes In patients given no temporary clipping, their postoperative activity in daily living (ADL) grade was good in 70.7%, i.e. ADL 1 or 2, whereas only 46.4% of the patients given a temporary clipping achieved a similar ADL. 2) Influence of the preoperative Hunt and Kosnik neurological classification on the outcome Irrespective of whether a temporary clip had been used, patients with a Hunt and Kosnik grade of 1 or 2 made a good recovery, whereas patients with a grade of 4 or 5 did not. The application of a temporary clip in grade 3 patients led to a poor result, whereas in grade 3 patients given no temporary clipping the results were good. This would seem to indicate that Hunt and Kosnik grade 3 rating is a critical factor in consideration whether a temporary clip should be used or not. 3) Influence of the operative timing on the outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed1992

[Assessment of coronary hemodynamics and myocardial perfusion in patients with syndrome X by digital subtraction angiography and 201Tl-myocardial scintigraphy].

To evaluate coronary hemodynamics and myocardial perfusion, left coronary digital subtraction angiography (DSA) and Tl-201 myocardial scintigraphy were performed in patients with syndrome X. The coronary circulation time (CCT) was significantly prolonged after the injection of isosorbide dinitrate and contrast medium i.c. Apical T1/2 was also prolonged on ergonovine malate provocation test. We suspected that the vascular response of the coronary peripheral artery was impaired, and microvascular spasm probably existed in patients with syndrome X. The prevalence of abnormal myocardial perfusion defect on exercise Tl-201 SPECT in syndrome X was very high, and coronary hemodynamics was significantly disturbed in the group of syndrome X with abnormal Tl-201 SPECT. Tl-201 lung/heart count ratio significantly increased in syndrome X on treadmill test. Because of this, exercise induced left ventricular dysfunction was suspected. We concluded that the main pathophysiological finding of impaired coronary circulation in syndrome X was microvascular spasm.

Angiography, Digital Subtraction↗
PubMed1991

Invasive human fibrosarcoma DNA mediated induction of a 92 kDa gelatinase/type IV collagenase leads to an invasive phenotype.

Proteolytic enzymes, such as gelatinase/type IV collagenase, play a pivotal role in cancer invasion and metastasis. Invasive human fibrosarcoma cells (HT1080) secrete two species of gelatinase/type IV collagenase, 68-72 kDa and 92 kDa enzymes. The purpose of this study is to elucidate which species of gelatinase/type IV collagenase plays a more important role in invasion. We have found that HT1080 x human fibroblast hybrids have reduced ability to invade a reconstituted basement membrane (Matrigel) in vitro compared to HT1080 cells, and abundantly secrete only the 68-72 kDa gelatinase/type IV collagenase. These data suggest that the 92 kDa gelatinase/type IV collagenase may be more important in HT1080 cell invasion. We next transfected HT1080 genomic DNA into non-invasive mouse C3H/10T1/2 fibroblast cells, which secrete only 68-72 kDa gelatinase/type IV collagenase. Four invasive transfectants were established. These invasive transfectants secreted the 92 kDa gelatinase/type IV collagenase in addition to the 68-72 kDa gelatinase/type IV collagenase, whereas non-invasive control DNA transfectants did not secrete the 92 kDa gelatinase/type IV collagenase. These results suggest that the induction of the 92 kDa gelatinase/type IV collagenase is important in the invasive phenotype.

Animals↗
PubMed1991

Functional conversion from HIV-1 Rev to HTLV-1 Rex by mutation.

A nucleolar localizing rev gene mutant M10 of human immunodeficiency virus type 1 (HIV-1) lost a Rev function completely, instead, gained a Rex activity of human T cell leukemia virus type 1 (HTLV-1). The obtained compatibility between Rev M10 and Rex with their own nucleolar targeting signal (NOS) suggests a common molecular mechanism of their post-transcriptional regulation, despite no sequence similarities of both proteins and their responsive RNA elements, respectively.

Amino Acid Sequence↗
PubMed1991

Transforming growth factor-beta suppresses the invasiveness of human fibrosarcoma cells in vitro by increasing expression of tissue inhibitor of metalloprotease.

We have investigated the effects of TGF-beta on the ability of the human fibrosarcoma cell line, HT1080, to invade a reconstituted basement membrane (Matrigel) in vitro. Exposure of HT1080 cells to TGF-beta (1-10ng/ml) caused a dose-dependent inhibition of HT1080 cell invasion. Unexpectedly, TGF-beta (10ng/ml) significantly enhanced (10-fold) the mRNA expression of the 68-72kDa latent type IV collagenase. Zymogram analysis revealed a 7-fold increase in the 68-72kDa latent type IV collagenase concomitant with an increase in the activated form (62kDa). TGF-beta induced the 92kDa type IV collagenase to a lesser degree. HT1080 cells exposed to TGF-beta also produced more tissue inhibitor of metalloprotease (TIMP) at both the mRNA (10-fold) and protein levels (5-fold). Although TGF-beta induced both type IV collagenases and TIMP, the net collagenolytic activity in the conditioned media after invasion assay was reduced in the presence of TGF-beta. The data suggest that the inhibition of invasiveness is due, at least in part, to the increased TIMP expression. These data suggest that TGF-beta may play a role in tumor cell invasion by increasing the expression of TIMP.

Cell Line↗
PubMed1991

Epidermal growth factor (EGF) expression in the congenital polycystic mouse kidney.

The mechanisms responsible for renal cyst formation in congenital polycystic kidney disease remain unknown, although abnormalities of cellular metabolism, basement membrane components, and growth factors have been suggested. In the present study, we examined a potential role for epidermal growth factor (EGF) in cyst formation in a mouse model. We measured growth factor activity and concentration in renal cyst fluid, urine, and serum obtained from mice with congenital polycystic kidney disease (cpk). In affected mice, both growth factor activity of urine and the urinary EGF concentration were much lower than unaffected littermate controls even when corrected for creatinine concentration. Although the growth factor activity was much lower in affected mice, there were significant differences in the regional distribution of EGF in animals with cysts. Both growth factor activity and EGF concentration were greater in cyst fluid when compared to urine. Growth factor activity in cysts was completely inhibited by anti-EGF antibody using BALB/MK epithelial keratinocytes as targets. The expression of EGF mRNA in kidneys from affected mice was markedly decreased when compared to littermate controls. These results suggest that decreased EGF production and local differences in EGF concentration may contribute to cyst formation.

Animals↗
PubMed1991

Effects of chimeric mutants of human immunodeficiency virus type 1 Rev and human T-cell leukemia virus type I Rex on nucleolar targeting signals.

Two chimeric mutant genes derived from rev of human immunodeficiency virus type 1 and rex of human T-cell leukemia virus type I were constructed to investigate the functions of the nucleolar-targeting signals (NOS) in Rev and Rex proteins. A chimeric Rex protein whose NOS region was substituted with the NOS of Rev was located predominantly in the cell nucleolus and functioned like the wild-type protein in the Rex assay system. However, a chimeric Rev with the NOS of Rex abolished Rev function despite its nucleolar localization. This nonfunctional nucleolar-targeting chimeric protein inhibited the function of both Rex and Rev. In the same experimental conditions, this mutant interfered with the localization of the functional Rex in the nucleolus.

Amino Acid Sequence↗
PubMed1991

Chromatin diminution and chromosome elimination in four Japanese hagfish species.

Cytogenetic examination of four Japanese hagfish species belonging to the order Myxinida (Eptatretus okinoseanus, E. burgeri. Paramyxine atami, and Myxine garmani) revealed differences in chromosome number between germ cells (spermatocytes and spermatogonia) and somatic cells (liver, blood, gill, and kidney). The differences in chromosome number between spermatogonia (54, 52, 48, and 16) and somatic cells (34, 36, 34, and 14) were 20, 16, 14, and 2 in E. okinoseanus, E. burgeri, P. atami, and M. garmani, respectively. The amount of DNA in a somatic cell (2C) relative to that in a germ cell (2C) averaged 54.6% (E. okinoseanus type A), 44.9% (E. okinoseanus type B), 79.1% (E. burgeri), 60.0% (P. atami), and 70.2% (M. garmani). These results clearly indicate that chromosome elimination takes place during early cleavage in the four hagfish species of Myxinida living in Japanese waters, except in the ancestral germline cells. C-banding of metaphase chromosome preparations of germline and somatic cells from each hagfish species revealed that the C-band-positive chromatin in the ancestral somatic cells had been almost completely eliminated. Three patterns of elimination of this chromatin are discussed.

Animals↗
PubMed1991

Development of bacillus Calmette-Guérin-induced antitumor activity in peripheral blood mononuclear cells.

Peripheral blood mononuclear cells (PBMNCs) after bladder instillation of bacillus Calmette-Guérin (BCG) to patients with superficial bladder carcinoma showed lytic activity against natural killer (NK)-sensitive and NK-resistant target tumor cells. PBMNCs in normal volunteers were isolated and cultured with BCG (5 micrograms/ml) in vitro. Maximum cytotoxicity was obtained within 24 h. Cytosine arabinoside as a DNA synthesis inhibitor did not inhibit this killer cell activation. Monoclonal antibody treatment revealed that both precursor and effector cells were NK cell type. However, effector cells had a wider spectrum of target cells than usual NK cells. The recognition specificity from cold target competition experiments was selective.

Administration, Intravesical↗