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Biomedical subjects

K Nitta

Publications and source records attributed to K Nitta.

At least 325 records · Page 18Linked to original sources

An in vitro screening method for antitumor and/or antitumorigenic substances involving the transformation of chick embryo fibroblasts infected with Rous sarcoma virus.

An efficient in vitro screening method for antitumor and/or antitumorigenic substances was established. The method is based on determining inhibitory effect of a compound on an RSV-induced tumorigenic process and the growth of the established tumor cells in a single assay system in the presence of normal cells. These effects were determined by inhibition of focus formation in a culture of chick embryo fibroblasts, while the nonspecific cytotoxic effect was determined by inhibition of the protein content of the same culture. The efficiency of this method in screening drugs was confirmed by testing various clinical and preclinical compounds.

Animals↗

Melting of local ordered structures in yeast 5S ribosomal RNA in aqueous salts.

Equilibrium and kinetics of thermal melting of yeast 5S ribosomal RNA in aqueous NaCl with or without Mg2+ were investigated by differential thermal melting and temperature jump methods. Two peaks (1 and 2) and a shoulder were observed in each of melting curves at ionic strength I=0.002-0.5 and linearity between each of melting temperatures T1m and T2m and log I was found at I=0.01-0.5 in the Mg2+-free solution. The local structures were found to be stabilized considerably by Mg2+. The temperature jump measurements gave the kinetic melting curve of the structure 1 at I=0.03 without Mg2+ or with 0.5 mM Mg2+. The kinetic Tm coincided well with the corresponding static Tm. For the structure 1, various parameters were calculated from the kinetic data, which indicated a double helical character of the structure 1. In terms of the values of Tm, G-C content, and enthalpy change of the transition of the structure 1 or 2, appropriateness of each of the secondary structure models of eukaryotic 5S RNA proposed previously was discussed.

Hot Temperature↗

[New direction in immunochemotherapy of cancer].

For the most effective cancer immunochemotherapy, the suppression of suppressive factors is very important as well as the activation of cytotoxic effector cells. We studied suppression of suppressor T cells with cancer chemotherapeutics at a usual dosage. One of our project teams showed that a single administration of bleomycin at 5 mg/kg to WKA rats vaccinated with irradiated syngeneic KMT-17 tumor cells before or after the vaccination strongly augmented the effect of the vaccination to give a good curability and ILS in the KMT-17 bearing rats, and that this effect of bleomycin resulted from suppression of suppressor cells. Another team of ours demonstrated a marked curable effect of combination therapy with cyclophosphamide and forphenicinol, a small molecular BRM, on syngeneic mammary adenocarcinoma in C3H/HeN mice producing a strong specific antitumor immunity after the cure. The third team showed that oxanosine, a new antitumor antibiotic, bore not only a direct tumoricidal activity but suppressor-suppressing and macrophage-activating activities. The fourth team studied cytoelectrophoresis of suppressor T cells and showed that immuno-specific suppressor T cells moved more slowly than non-stimulated normal T cells, the peak coming between the peaks of normal T cells (high mobility) and B cells (low mobility). This finding is useful for development of a new assay method for Ts-suppressing drugs. This group also studied a new screening method for inhibitors of non-specific suppressor T cells. There are several other approaches to cancer immunochemotherapy, which will be presented at other opportunities.

Adjuvants, Immunologic↗

[In vivo uptake of Ga-67 citrate by an experimental abscess and the mechanism of Ga-67 uptake].

This study was undertaken to investigate the accumulation of 67Ga in an experimental abscess and to elucidate the mechanism of 67Ga uptake in the abscess. Two, three, five, seven and ten days after subcutaneous injection of 0.2 ml turpentine to the rats, 67Ga-citrate was injected to the rats. Twenty-four hours after injection of 67Ga, abscess and organs were excised and uptake rates of 67Ga were assayed. Furthermore, five days after subcutaneous injection of 0.2 ml turpentine to the rats, 67Ga-citrate was injected to the rats, at various time intervals from 10 minutes to 6 days, abscess and organs were excised and uptake rates of 67Ga were assayed. And subcellular distribution of 67Ga in abscess was determined at various time intervals after administration of 67Ga-citrate. On the other hand, to elucidate 67Ga binding substances in abscess, 67Ga-citrate and sodium sulfate-35S were injected to the above rats, respectively. Twenty-four hours after injection, abscess was excised and homogenized. The homogenate was digested with proteinase. After digestion, the reaction mixture was gel-filtered on Sephadex G-100. Eluate samples were assayed for radioactivity, uronic acid and protein. Uptake rates of 67Ga in abscess increased with time after injection of turpentine and reached a plateau 5-7 days later. Ten minutes, 24 hours and 72 hours after injection of 67Ga, uptake rates of 67Ga in abscess were 0.92%/g, 3.3%/g and 5.6%/g, respectively. Uptake rates of 67Ga (24 hours after injection) in abscess was 2.0-3.4 time of tumor uptake rates (previously reported).(ABSTRACT TRUNCATED AT 250 WORDS)

Abscess↗

Induction of murine tumors in adult mice by a combination of either avian sarcoma virus or human adenovirus and syngeneic mouse embryo cells.

Primary murine Rous sarcoma was produced in adult mice of seven strains, C57BL/6, DBA/2, BALB/c, C3H/He, CBAJ, AKR, and DDD, by s.c. inoculation of a mixture of 5 X 10(6) chicken tumor cells containing Schmidt-Ruppin Rous sarcoma virus and 9- to 12-day-old mouse embryo cells (MEC) (2 X 10(6) ) of the syngeneic strain. The sarcoma developed at the site of injection in almost all mice tested, but there were some differences in the latent period and the survival time among mouse strains. When the number of cells inoculated was reduced to 5 X 10(4) for chicken tumor cells induced by the Schmidt-Ruppin strain of Rous sarcoma virus (SR-CTC) and 2 X 10(4) for MEC, no tumor was produced in C3H/He mice. These tumors had strain specificity and the Schmidt-Ruppin strain of Rous sarcoma virus genome in masked form. The tumor at the site of injection originated in the embryo cells injected along with SR-CTC. This was confirmed by CBAT6/T6 marker chromosome analysis of the tumor cells of CBA mice induced with SR-CTC plus CBAT6/T6 MEC and also confirmed by transplantation of a C57BL/6 X C3H/He F1 tumor which had been induced with SR-CTC plus C3H/He or C57BL/6 MEC. Tumor induction in adult mouse by a mixture of virus and syngeneic 9- to 14-day-old embryo cells was tested for human adenovirus serotype 12 (Ad12) and simian virus 40. Primary Ad12 tumor was also induced in adult CBA, C3H/He, and DDD mice by 4 X 10(5 to 6) 50% tissue culture infective dose of Ad12 with 5 X 10(6) syngeneic embryo cells. This tumor contained Ad12 T-antigen-positive particles in cells. But in the case of simian virus 40, the tumor did not appear for about 300 days of observation.

Age Factors↗

Antitumor activity of tetrahydro-2-furanyl- and tetrahydro-2-pyranyl-glucans obtained by chemical modification of (1 leads to 3)-beta-D-glucan from Alcaligenes faecalis var. myxogenes IFO 13140 and its lower molecular weight glucans.

The well-defined (1 leads to 3)-beta-D-glucan with DP (degree of polymerization) 540 and the various chain-length (1 leads to 3)-beta-D-glucans prepared by its hydrolysis were chemically modified to furanyl- and pyranyl-derivatives. As a primary screening, the effect of 20 derivatives thus obtained was tested on Sarcoma 180 solid tumor transplanted sc into allogeneic ICR mice; the dose was 10 mg/kg ip for 10 days. Eleven derivatives that showed a strong antitumor effect on Sarcoma 180 were also tested on Meth-A solid tumor in syngeneic mice. Of the derivatives tested, five furanyl-derivatives (F-4, F-6, F-7, F-10, and F-11) and one pyranyl-derivative (P-5) had potent antitumor effects on this syngeneic tumor system at ip doses of 10 or 30 mg/kg for 10 days. By oral administration, only two derivatives (F-10 and P-3) showed moderate antitumor activity against Sarcoma 180, without complete tumor regression. The mechanism of action of these derivatives was considered to be host-mediated and similar to that of the original glucan, because of a lack of effect in vitro.

Alcaligenes↗

Superoxide anion production from mouse peritoneal macrophages stimulated with surface-bound IgG and immune complexes: adsorption characteristics of IgG in relationship to biological activity.

The bridging of IgG antibody molecules by either multivalent antigen or protein A adsorbed to a polymer surface triggers superoxide anion (O-2) generation from mouse peritoneal macrophages. Macrophages, upon stimulation with IgG adsorbed to a hydrophobic polymer, polystyrene, also significantly generated O-2. In contrast, soluble IgG did not stimulate macrophages. From these results we speculated that IgG adsorbed to polystyrene produces the same kind of a conformational change in its Fc region as seen in immune complexes, and leads to enhancement of the ability of the Fc region to bind macrophage Fc receptors, acting as a multivalent cross-linking agent to aggregate the Fc receptors. The surface charge density of the immunosorbent did not affect the antigen recognition function of antibody, but markedly affected its effector function. These findings suggest that activation of the Fc receptor-mediated function of macrophages requires, on the one hand, optimal conformational change and orientation of IgG and immune complexes adsorbed to the polymer surface and, on the other hand, the bridging of IgG molecules by multivalent agents.

Adsorption↗

Action of a new antibiotic, neo-enactin, on the cell membrane and its application to combination treatment in a cultured tumor cell system.

Neo-enactin, a new antibiotic obtained from a Streptoverticillium, was found to act on the eukaryotic cell membrane and induce changes in the transport of molecules across the cell membrane. Neo-enactin markedly potentiated the action of the antitumor agents bleomycin and vincristine in vitro. The uptake of [14C]vincristine by HeLa cells was enhanced 3.4-fold in the presence of neo-enactin. It is suggested that the potentiation of a second drug by neo-enactin may result from enhanced permeation of that drug.

Animals↗

[Transthoracic catheterization under monitoring by ultrasono-cardiotomography and its clinical usefulness].

When serious postoperative complications such as mechanical malfunction of the implanted valve occur in patients with multiple valvular replacements, it is very urgent to evaluate the function of the valve and heart and to establish an accurate diagnosis as to the damaged prosthetic valve, while giving intensive life-saving bed-side care. Under such circumstances, transvascular heart catheterization necessary for obtaining hemodynamic data or for angiocardiography can not be applied because it is almost impossible for a catheter to pass through a prosthetic valve without potential danger. Then, the present authors have introduced a method of cardiac catheterization by a direct transthoracic route during which cardiac structures are monitored by ultrasono-cardiotomography. This method is called "transthoracic catheterization monitored by ultrasono-cardiotomography," and was applied to cases of double (aortic and mitral) valve replacements. The immobile adhesive area in the vicinity the right ventricular wall is detected from the longitudinal or horizontal cross-section pictures, through which a polyethylene catheter with stylet was introduced from the subxiphoid region and was advanced toward the left ventricle. After introduction of the catheter into the right ventricle, the catheter tip was advanced to the midportion of the ventricular septum, which was selected to avoid the penetration of the tricuspid valve and coronary arteries. Then, the catheter was passed into the left ventricle on the ultrasonic scanning plane along the direction of the short axis of the heart. After placing the catheter into the left ventricle, a small amount of contrast material was injected to confirm the precise positioning of the catheter tip in the left ventricle. Thus, the hemodynamic measurement and angiocardiograpy were performed easily. By utilizing contrast cardiotomography, valvular function was evaluated easily without any side effects as in case of angiocardiography. Furthermore, ultrasono-cardiotomography was sensitive in detecting cardiac tamponade if appeared during direct heart catheterization, making immediate treatment possible. Thus, transthoracic catheterization monitored by ultrasono-cardiotomography was useful for the evaluation of the function of the prosthetic valve, especially in cases with double valve prostheses.

Adult↗

[Experimental studies on antitumor effects of lysozyme-II. Effect of lysozyme on immunopotentiation].

Effects of lysozyme (LY) on immuno-responses were examined. Tumor-bearing mice were used on most of experiments and normal mice on several cases of experiments. Cytostatic activity on the Peyer's patch cells in Meth-A bearing Balb/c mice was enhanced at 6 to 12 hrs after oral administration of LY. Furthermore, LY showed to recover from the decline of blastogenic activity, which was observed on the lymph node cells and the spleen cells of tumor-bearing mice, at 8 and 14 days after tumor inoculation. In the normal ICR mice, it was not observed that LY increased the foot-pad reaction against the sheep red blood cells (SRBC). On the other hand, the decrease of the foot-pad reaction, which was observed in the tumor bearing mice at 20 days after Sarcoma-180 (S-180) inoculation, was recovered by the administration of LY. A decrease of the number of plaque-forming cells (PFC) against SRBC which was induced with tumor inoculation in the spleen cells was not observed at 20 days after S-180 inoculation, but LY caused a significant increase of PFC response in spleens on both of normal and tumor bearing mice. From these results, it was suggested that potentiation of systemic immuno-response derived from the activation of Peyer's patches brought about antitumor effects of LY.

Adjuvants, Immunologic↗

[Experimental studies on antitumor effects of lysozyme].

Effects of lysozyme(LY) alone and combination with various antitumor agents were examined using syngeneic tumors mainly Meth-A and MH 134 transplanted into Balb/c and C3H/He mice, respectively. The effects of LY on pulmonary metastases were also examined in BDF1 mice bearing Lewis lung carcinoma (3LL). LY inhibited the growth of Meth-A tumor and enhanced antitumor effects of mitomycin C (MMC). bleomycin (BLM) and 5-fluorouracil (5-FU), LY activated antitumor effects of MMC, BLM and 5-FU on MH 134 tumor, however, LY alone did not show any significant antitumor effect on it. The combination treatments using LY with MMC or 5-FU showed a marked inhibition on pulmonary metastases of 3LL. The pre-treatment of LY inhibited the tumor growth of Sarcoma-180 in ICR mice.

Animals↗

A murine B-cell lymphoma induced by Gross virus.

A B-lymphocyte tumor (MLB-MN line) was induced by Gross murine leukemia virus in Slc:ddY mice, successively passaged in normal adult mice, and adapted to tissue culture. The surface marker expression of MLB-MN was examined and found to include several markers that are known to occur in normal B-lymphocytes. The cells bore surface immunoglobulin M, detected by indirect immunofluorescence staining, and Fc receptors and complement receptors, detected by rosette formation. Thy 1 antigen and secretion of immunoglobulin were lacking. These results have led us to postulate that the origin of the MLB-MN tumor was a late differentiation stage of the B-lymphocyte.

AKR murine leukemia virus↗