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Biomedical subjects

K Nitta

Publications and source records attributed to K Nitta.

At least 289 records · Page 16Linked to original sources
PubMed1987

[Antitumor activity of new derivatives of camptothecin].

With the purpose of obtaining more potent and less toxic camptothecin (CPT) analogs, we prepared many derivatives of CPT. Among them, 7-ethyl-CPT (SN 22) and 7-ethyl-10-hydroxy-CPT (SN 38) showed strong antitumor activity with less toxicity. They were, however, insoluble and when they were made soluble, their activity was markedly diminished, as a result of cleavage of the delta-lactone ring. We therefore attempted to make soluble derivatives without breaking the delta-lactone ring and obtained 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxy-CPT (CPT-11), which showed very strong antitumor activity by i.p., i.v. or p.o. administration against the ascites type of L1210 leukemia, P388 leukemia, sarcoma 180, Meth A fibrosarcoma, B16 melanoma, Ehrlich carcinoma and MH134 hepatoma and the solid type of sarcoma 180, Meth A fibrosarcoma, Lewis lung carcinoma, C3H/HeN mammary carcinoma, Ehrlich carcinoma and MH134 hepatoma. The antileukemic activity of CPT-11 against L1210 was much higher than that of adriamycin. The acute toxicity of CPT-11 was extremely low, particularly in the case of oral administration, the LD50 being 765.3 mg/kg, 22 times greater than that of CPT-Na.

Animals↗
PubMed1987

Recombinant human tumor necrosis factor depresses serum iron in mice.

Recently many findings about the physiological and biochemical functions of recombinant human tumor necrosis factor (rHu-TNF) have been reported. In the present study, the effect of rHu-TNF on serum iron in C3H/HeN and C57BL/6 mice was determined. Blood samples were obtained before intravenous injection of rHu-TNF, and also at various times after the injection. Results from five experiments showed that the serum iron was depressed between 1/3 to 1/5 of that of untreated mice 4 to 24 h after injection of 5 or 10 micrograms of rHu-TNF. The low level persisted for 33 h, rebounded at 48 to 72 h, and returned to normal by 96 h after the injection. Serum iron was determined by the colorimetric method using the sensitive reagent, ferrozine (3-(2-pyridyl)-5,6-bis(4-sulfophenyl)-1,2,4-triazine. We believe that this is the first report of depression of serum iron in mice by intravenous injection of rHu-TNF. The physiological role of repressed serum iron in the in vivo response to TNF remains to be established.

Animals↗
PubMed1986

Ontogeny of calcitonin gene-related peptide and calcitonin in the rat thyroid.

In this immunohistochemical study, the ontogenic development of calcitonin-gene-related peptide (CGRP) in the rat thyroid was investigated and compared with that of calcitonin using the indirect-immunofluorescence method. Parafollicular cells with immunoreactivity to both CGRP and calcitonin first appeared at an early stage of gestation (days 17 and 18) in the central portion of the thyroid. Cells immunoreactive to CGRP and calcitonin had became numerous by gestational day 22. After postnatal day 7, CGRP- and calcitonin-immunoreactive (C-IR) cells increased rapidly both in number and in the intensity of their fluorescence. In 14- to 90-day old rats, many intensely immunoreactive cells were distributed in the central portion of the thyroid. The cells immunoreactive to CGRP and to calcitonin had an almost identical ontogenic appearance. In 14-day-old and adult rats, C-IR cells also exhibited CGRP immunostaining, suggesting that these cells simultaneously produce and store CGRP during ontogeny.

Aging↗
PubMed1986

Rapid tumor regression and induction of tumor-regressing activity in serum by various immune-modulating agents.

A rapid decrease in the number of tumor cells from S180 tumors was caused by several antitumor polysaccharides including the beta (1-3)glucans lentinan and TAK-N and a mannoglucan MGA, but not by those lacking antitumor activity. MGA was demonstrated to induce potent tumor-regressing activity in the serum of tumor-bearing mice similar to that reported previously to be induced after an injection of CM-TAK, a carboxymethylated beta (1-3)glucan. It is probable that the induction of rapid regression of established tumors is a phenomenon common to antitumor polysaccharides and some microbiological products and that the tumor-regressing factor in the serum underlies a common mechanism.

Animals↗
PubMed1986

Binding strength of calcium ion to bovine alpha-lactalbumin.

A Ca2+-sensitive electrode was used for determination of the binding strength of Ca2+ to bovine alpha-lactalbumin in 60 mM Tris buffer (pH 7.8-8.5) in the presence of various concentrations of NaCl. The dependence of the apparent binding constant on the concentration of NaCl was consistent with competitive binding of Ca2+ and Na+, and the binding constants of Ca2+ and Na+ were found to be 2.2 (+/- 0.5) X 10(7) M-1 and 99 (+/- 33) M-1, respectively, at 37 degrees C and pH 8.0. The temperature dependence of the binding constant of Ca2+ was examined between 30 and 45 degrees C; extrapolation of the dependence led to a binding constant of approximately 1 X 10(8) M-1 at pH 8.4 and 25 degrees C. The electrostatic contribution and conformational effect of the protein were also taken into consideration, and the intrinsic binding constant of Ca2+ to native alpha-lactalbumin was calculated to be (1.2-1.5) X 10(10) M-1 at 37 degrees C and pH 8.0.

Animals↗
PubMed1986

Effects of mannitol on cerebral circulation after transient complete cerebral ischemia in dogs.

The effects of hypertonic mannitol on postischemic cerebral circulation were studied in 20 dogs. Mannitol, 2 g/kg iv, was infused into ten dogs during a 2-h period starting 1.5 h after 6 min of complete cerebral ischemia. One hour postischemia, regional cerebral blood flow (rCBF) was 36% in the control group (ten dogs) and 39% in the mannitol group. In the control group, rCBF increased gradually thereafter to 70% of the preischemic value 10 h postischemia, whereas the restoration of rCBF was suppressed in the mannitol group. During the postischemic period, intracranial pressure (ICP) increased significantly in the control group, but it did not change significantly in the mannitol group. The effects of mannitol on rCBF and ICP in the present study can be explained primarily by decreased body water due to urinary loss. The administration of mannitol does not necessarily improve postischemic cerebral circulation.

Animals↗
PubMed1986

[Enhancement of immune response by an antitumor agent, cyclophosphamide].

Cyclophosphamide (CY) is an agent with one of the broadest antitumor spectra in cancer chemotherapy. CY was chosen because its effectiveness in tumor immunity in combination with other agents (BCG or FPL) had been shown in our previous experiments. The effect of CY on the immuno-regulatory system is diverse, depending on a multitude of factors including the type of immune response measured, the antigen, the dose of the drug, the time of its administration in relation to antigen, etc. Thus, we investigated the effect of CY on suppressive factors using an adoptive transfer approach in both DTH reaction and tumor immunity. The results indicated that CY would eliminate suppressor cells regulating cellular responses in DTH reaction and tumor immunity in a variable manner.

Animals↗
PubMed1986

Cell-mediated immune response in mice during the two-step carcinogenesis experiment by 7,12-dimethylbenz(a)anthracene and 12-O-tetradecanoylphorbol-13-acetate.

Cell mediated immune response in ICR mice during the two step carcinogenesis experiment induced by DMBA plus TPA was followed by determining the delayed type hypersensitivity to two antigens, i.e. DNFB applied to skin and SRBC injected intraperitoneally. In mice developing tumors from 3 to 15 weeks after DMBA initiation, delayed type hypersensitivity to DNFB was suppressed to as low as 30% that of normal mice. This suppression was not recovered by treatment of indomethacin. No difference in delayed type hypersensitivity to SRBC was observed on between the mice on the two-step carcinogenesis experiment and normal mice.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

[Inhibition of the development of thermotolerance by combined treatment with an anticancer drug or benzylidene glucopyranose with the hyperthermia].

Transitional thermotolerance develops during (at below circa 43 degrees C) or after (at above circa 43 degrees C) hyperthermic treatment, increases through the first 6 h, is maintained for circa 24 h and disappears at circa 72 h after the hyperthermia. Therefore, a once every three days modality of hyperthermic treatment is preferred among the clinical institutions where therapeutic hyperthermia is provided. In the present communication, the inhibition of thermotolerance development by combined treatment of anticancer drug or benzylidene glucopyranose with hyperthermia and its related problems are reported.

Animals↗
PubMed1986

Conformation of B. stearothermophilus 5S ribosomal RNA.

The thermal melting of B. stearothermophilus 5S ribosomal RNA was studied, by means of derivative optical absorption and CD spectra, and high performance liquid chromatography, in Tris buffers with K+ and Mg2+ at pH 7.6. Biphasic changes in optical absorption and CD ellipticity were observed, which mean the melting of two helices. Change in molecular size was also examined in the melting process. The melting temperatures depended on ionic strength and concentration of Mg2+. Enhanced stability of the helix was indicated, as compared with the corresponding one in B. subtilis 5S ribosomal RNA. In the presence of a large amount of Mg2+, the third melting process was observed at low temperatures, which was suggested due to change in the tertiary structure.

Circular Dichroism↗
PubMed1986

Retention and subcellular distribution of 67Ga in normal organs.

Using normal rats, retention values and subcellular distribution of 67Ga in each organ were investigated. At 10 min after administration of 67Ga-citrate the retention value of 67Ga in blood was 6.77% dose/g, and this value decreased with time. The values for skeletal muscle, lung, pancreas, adrenal, heart muscle, brain, small intestine, large intestine and spinal cord were the highest at 10 min after administration, and they decreased with time. Conversely, this value in bone increased until 10 days after injection. But in the liver, kidney, and stomach, these values increased with time after administration and were highest 24 h or 48 h after injection. After that, they decreased with time. The value in spleen reached a plateau 48 h after administration, and hardly varied for 10 days. From the results of subcellular fractionation, it was deduced that lysosome plays quite an important role in the concentration of 67Ga in small intestine, stomach, lung, kidney and pancreas; a lesser role in its concentration in heart muscle, and hardly any role in the 67Ga accumulation in skeletal muscle. In spleen, the contents in nuclear, mitochondrial, microsomal, and supernatant fractions all contributed to the accumulation of 67Ga.

Animals↗
PubMed1986

Antitumor polysaccharide-induced tumor-regressing factor in the serum of tumor-bearing mice: purification and characterization.

Marked tumor-regressing activity was induced in the serum of S180 tumor-bearing mice by injection of an antitumor polysaccharide, CM-TAK [carboxymethylated beta(1-3)glucan]. Maximal activity was induced 7-14 days after the tumor transplantation and 10-12 h after CM-TAK treatment. A quantitative assay for the activity was established on the basis of the initial decrease in the number of the tumor cells within 24 h. The factor with tumor-regressing activity was purified 10,000-fold by the series of hydroxylapatite chromatography, ammonium sulfate precipitation, anion-exchange chromatography, gel filtration, and boronate-mediated affinity chromatography. The molecular weight was estimated to be 250,000 by gel filtration. The activity was proteinase K sensitive, but relatively resistant to trypsin. Neuraminidase did not affect the activity. It is believed that the tumor-regressing factor is different from the tumor necrosis factor.

Alcaligenes↗
PubMed1986

Rapid tumor regression caused by antitumor polysaccharide and induction of tumor-regressing factor in the serum of tumor-bearing mice.

The antitumor polysaccharide CM-TAK [carboxymethylated beta(1-3)glucan] caused immediate and rapid loss of viable tumor cells from S180 solid tumors in ICR mice if it was given after a week of tumor growth. We found marked tumor-regressing activity in the serum of mice with S180 tumors undergoing CM-TAK-induced regression. When injected intravenously into S180-bearing mice, 0.1 ml of serum/mouse induced complete regression of day-14 tumors. However, in vitro cytotoxic activity against L929 and S180 cells was not detected. After the injection of CM-TAK or serum, along with the rapid decrease in tumor cells there was a marked increase in polymorphonuclear leukocytes. The serum was also active against fibrosarcoma Meth A in BALB/c mice, inducing partial regression or significant decrease in growth of the tumor. The properties of the factor in the serum seem to be different from those reported for tumor-necrotizing factor and other endogenous cytotoxic substances.

Animals↗